Peptide nanostructures and methods of generating and using the same

ABSTRACT

A tubular or spherical nanostructure composed of a plurality of peptides, wherein each of the plurality of peptides includes no more than 4 amino acids and whereas at least one of the 4 amino acids is an aromatic amino acid.

This is a continuation in part of PCT/IL03/01045, filed Dec. 9, 2003,which claims priority of U.S. Provisional Patent Application Nos.60/431,709, filed Dec. 9, 2002 and 60/458,378, filed Mar. 31, 2003. Thisapplication also claims priority of U.S. Provisional Patent ApplicationNos. 60/607,588, filed Sep. 8, 2004 and 60/592,523, filed Aug. 2, 2004.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to peptide nanostructures and methods ofgenerating and using same.

Nanoscience is the science of small particles of materials and is one ofthe most important research frontiers in modern technology. These smallparticles are of interest from a fundamental point of view since theyenable construction of materials and structures of well-definedproperties. With the ability to precisely control material propertiescome new opportunities for technological and commercial development, andapplications of nanoparticles have been shown or proposed in areas asdiverse as micro- and nanoelectronics, nanofluidics, coatings and paintsand biotechnology.

Numerous configurations have been proposed and applied for theconstruction of nanostructures. Most widely used are the fullerenecarbon nanotubes. Two major forms of carbon nanotubes exist,single-walled nanotubes (SWNT), which can be considered as long wrappedgraphene sheets and multi walled nanotubes (MWNT) which can beconsidered as a collection of concentric SWNTs with different diameters.

SWNTs have a typical length to diameter ratio of about 1000 and as suchare typically considered nearly one-dimensional. These nanotubes consistof two separate regions with different physical and chemical properties.A first such region is the side wall of the tube and a second region isthe end cap of the tube. The end cap structure is similar to a derivedfrom smaller fullerene, such as C₆₀.

Carbon nanotubes produced to date suffer from major structurallimitations. Structural deviations including Y branches, T branches orSWNT junctions, are frequent results of currently used synthesisprocesses. Though such deviations in structure can be introduced in a“controlled” manner under specific conditions, frequent uncontrollableinsertion of such defects result in spatial structures withunpredictable electronic, molecular and structural properties.

Other well-studied nanostructures are lipid surfactant nanomaterials(e.g., diacetylene lipids) which self-assemble into well-orderednanotubes and other bilayer assemblies in water and aqueous solution[Yager (1984) Mol. Cryst. Liq. Cryst. 106:371-381; Schnur (1993) Science262:1669-1676; Selinger (2001) J. Phys. Chem. B 105:7157-7169]. Oneproposed application of lipid tubules is as vehicles for controlled drugrelease. Accordingly, such tubes coated with metallic copper and loadedwith antibiotics were used to prevent marine fouling.

Although lipid-based nanotubules are simple in form, lipid structuresare mechanically weak and difficult to modify and functionalize, thusrestricting their range of applications.

Recently, peptide building blocks have been shown to form nanotubes.Peptide-based nanotubular structures have been made through stacking ofcyclic D-, L-peptide subunits. These peptides self-assemble throughhydrogen-bonding interactions into nanotubules, which in-turnself-assemble into ordered parallel arrays of nanotubes. The number ofamino acids in the ring determines the inside diameter of the nanotubesobtained. Such nanotubes have been shown to form transmembrane channelscapable of transporting ions and small molecules [Ghadiri, M. R. et al.,Nature 366, 324-327 (1993); Ghadiri, M. R. et al., Nature 369, 301-304(1994); Bong, D. T. et al., Angew. Chem. Int. Ed. 40, 988-1011 (2001)].

More recently, the discovery of surfactant-like peptides that undergospontaneous assembly to form nanotubes with a helical twist has beenmade. The monomers of these surfactant peptides, like lipids, havedistinctive polar and nonpolar portions. They are composed of 7-8residues, approximately 2 nm in length when fully extended, anddimensionally similar to phospholipids found in cell membranes. Althoughthe sequences of these peptides are diverse, they share a commonchemical property, i.e., a hydrophobic tail and a hydrophilic head.These peptide nanotubes, like carbon and lipid nanotubes, also have avery high surface area to weight ratio. Molecular modeling of thepeptide nanotubes suggests a possible structural organization [Vauthey(2002) Proc. Natl. Acad. Sci. USA 99:5355; Zhang (2002) Curr. Opin.Chem. Biol. 6:865]. Based on observation and calculation, it is proposedthat the cylindrical subunits are formed from surfactant peptides thatself-assemble into bilayers, where hydrophilic head groups remainexposed to the aqueous medium. Finally, the tubular arrays undergoself-assembly through non-covalent interactions that are widely found insurfactant and micelle structures and formation processes.

Peptide based bis(N-α-amido-glycyglycine)-1,7-heptane dicarboxylatemolecules were also shown to be assembled into tubular structures[Matsui (2000) J. Phys. Chem. B 104:3383].

When the crystal structure of di-phenylalanine peptides was determined,it was noted that hollow nanometric channels are formed within theframework of the macroscopic crystal [Gorbitz (2001) Chemistry7(23):5153-9]. However, no individual nanotubes could be formed bycrystallization, as the crystallization conditions used in this studyincluded evaporation of an aqueous solution at 80° C. No formation ofdiscrete nano-structures was reported under these conditions.

As mentioned hereinabove, peptide nanotubes contributed to a significantprogress in the field of nanotechnology since such building blocks canbe easily modified and used in numerous mechanical, electrical,chemical, optical and biotechnological systems.

The development of systems which include nanoscale components has beenslowed by the unavailability of devices for sensing, measuring andanalyzing with nanometer resolution. One class of devices that havefound some use in nanotechnology applications are proximity probes ofvarious types including those used in scanning tunneling microscopes,atomic force microscopes and magnetic force microscopes. While goodprogress has been made in controlling the position of the macroscopicprobe to sub-angstrom accuracy and in designing sensitive detectionschemes, the tip designs to date have a number of problems.

One such problem arises from changes in the properties of the tip asatoms move about on the tip, or as the tip acquires an atom or moleculefrom the object being imaged. Another difficulty with existing probemicroscope tips is that they typically are pyramidal in shape, and thatthey are not able to penetrate small openings on the object beingimaged. Moreover, existing probe microscopes often give false imageinformation around sharp vertical discontinuities (e.g., steps) in theobject being imaged, because the active portion of the tip may shiftfrom the bottom atom to an atom on the tip's side.

An additional area in which nanoscience can play a role is related toheat transfer. Despite considerable previous research and developmentfocusing on industrial heat transfer requirements, major improvements incooling capabilities have been held back because of a fundamental limitin the heat transfer properties of conventional fluids. It is well knownthat materials in solid form have orders-of-magnitude larger thermalconductivities than those of fluids. Therefore, fluids containingsuspended solid particles are expected to display significantly enhancedthermal conductivities relative to conventional heat transfer fluids.

Low thermal conductivity is a primary limitation in the development ofenergy-efficient heat transfer fluids required in many industrialapplications. To overcome this limitation, a new class of heat transferfluids called nanofluids has been developed by suspendingnanocrystalline particles in liquids such as water, oil, or ethyleneglycol. The resulting nanofluids possess extremely high thermalconductivities compared to the liquids without dispersed nanocrystallineparticles. Excellent suspension properties are also observed, with nosignificant settling of nanocrystalline oxide particles occurring instationary fluids over time periods longer than several days. Directevaporation of copper nanoparticles into pump oil results in similarimprovements in thermal conductivity compared to oxide-in-water systems,but importantly, requires far smaller concentrations of dispersednanocrystalline powder.

Numerous theoretical and experimental studies of the effective thermalconductivity of dispersions containing particles have been conductedsince Maxwell's theoretical work was published more than 100 years ago.However, all previous studies of the thermal conductivity of suspensionshave been confined to those containing millimeter- or micron-sizedparticles. Maxwell's model shows that the effective thermal conductivityof suspensions containing spherical particles increases with the volumefraction of the solid particles. It is also known that the thermalconductivity of suspensions increases with the ratio of the surface areato volume of the particle. Since the surface area to volume ratio is1000 times larger for particles with a 10 nm diameter than for particleswith a 10 mm diameter, a much more dramatic improvement in effectivethermal conductivity is expected as a result of decreasing the particlesize in a solution than can obtained by altering the particle shapes oflarge particles.

It is recognized that peptide nanotubes are natural candidates forperforming the above and many other tasks in the field ofnanotechnology.

However, currently available peptide nanotubes are composed of peptidebuilding blocks, which are relatively long and as such are expensive anddifficult to produce, or limited by heterogeneity of structures that areformed as bundles or networks rather than discrete nanoscale structures.

There is thus a widely recognized need for, and it would be highlyadvantageous to have, a peptide nanostructure, which is devoid of theabove limitations.

SUMMARY OF THE INVENTION

According to one aspect of the present invention there is provided atubular, spherical or planar nanostructure composed of a plurality ofpeptides, wherein each of the plurality of peptides includes at leastone aromatic amino acid in the case of peptides that consists of no morethan 4 amino acids and aromatic polypeptides which are composed solelyfrom aromatic amino acids.

According to another aspect of the present invention there is provided amethod of generating a tubular, spherical or planar nanostructure, themethod comprising incubating a plurality of peptide molecules underconditions which favor formation of the tubular, spherical or planarnanostructure, wherein each of the peptide molecules includes no morethan 4 amino acids and whereas at least one of the 4 amino acids is anaromatic amino acid.

According to further features in preferred embodiments of the inventiondescried below, the conditions which favor formation the tubular,spherical or planar nanostructure are selected from the group consistingof a solution type, concentration of the peptide molecules, aggregationtime, non-evaporating conditions and temperature

According to yet another aspect of the present invention there isprovided a field emitter device, comprising an electrode and ananostructure being composed of a plurality of peptides, the electrodeand the nanostructure being designed and constructed such that when anelectrical field is formed therebetween, electrons are emitted from thenanostructure, wherein each of the plurality of peptides of thenanostructure includes no more than 4 amino acids and wherein at leastone of the 4 amino acids is an aromatic amino acid.

According to further features in preferred embodiments of the inventiondescried below, the field emitter device further comprises a substratehaving a fluorescent powder coating, the fluorescent powder coatingbeing capable of emitting light upon activation by the electrons.

According to still another aspect of the present invention there isprovided a device for obtaining information from a nanoscaleenvironment, the device comprising: (a) a nanostructure capable ofcollecting signals from the nanoscale environment, the nanostructurebeing composed of a plurality of peptides each including no more than 4amino acids, wherein at least one of the 4 amino acids is an aromaticamino acid; and (b) a detection system capable of interfacing with thenanostructure and receiving the signals thus obtaining information fromthe nanoscale environment.

According to further features in preferred embodiments of the inventiondescried below, the device for obtaining information further comprises asupporting element onto which the nanostructure being mounted, whereinthe supporting element is operable to physically scan the nanoscaleenvironment.

According to still further features in the described preferredembodiments the nanostructure is adapted to collect near field lightfrom the nanoscale environment.

According to still further features in the described preferredembodiments the detection system is capable of converting physicalmotion of the nanostructure to electric signals.

According to an additional aspect of the present invention there isprovided an apparatus for electron emission lithography, comprising: (a)an electron emission source being at a first electrical potential, theelectron emission source including at least one nanostructure beingcomposed of a plurality of peptides each including no more than 4 aminoacids, wherein at least one of the 4 amino acids is an aromatic aminoacid; and (b) an electrically conducting mounting device being in asecond electrical potential, the second electrical potential beingdifferent than the first electrical potential; wherein a differencebetween the second electrical potential and the first electricalpotential is selected such that electrons are emitted from the electronemission source, and impinge on the mounting device to thereby perform alithography process on a sample mounted on the mounting device.

According to further features in preferred embodiments of the inventiondescried below, the apparatus further comprises a magnetic fieldgenerator for generating a magnetic field, thereby to direct theelectrons to a predetermined location on the sample.

According to yet an additional aspect of the present invention there isprovided a memory cell, comprising: (a) an electrode; and (b) ananostructure composed of a plurality of peptides each including no morethan 4 amino acids at least one of which being an aromatic amino acid,the nanostructure being capable of assuming one of at least two states;the nanostructure and the electrode being designed and constructed suchthat when electrical current flows through the electrode, thenanostructure transforms from a first state of the at least to states toa second state of the at least to states.

According to further features in preferred embodiments of the inventiondescried below, the transformation from the first state to the secondstate comprises a geometrical deflection of the nanostructure.

According to still an additional aspect of the present invention thereis provided a mechanical transmission device, comprising a firstnanostructure and a second nanostructure, the first and the secondnanostructure being operatively associated thereamongst such that amotion of the first nanostructure generates a motion of the secondnanostructure, wherein at least one of the first and the secondnanostructures is composed of a plurality of peptides each includes nomore than 4 amino acids, wherein at least one of the 4 amino acids is anaromatic amino acid.

According to a further aspect of the present invention there is provideda nanoscale mechanical device, comprising at least one nanostructuredesigned and configured for grabbing and/or manipulating nanoscaleobjects, wherein the at least one nanostructures is composed of aplurality of peptides each including no more than 4 amino acids, whereinat least one of the 4 amino acids is an aromatic amino acid.

According to further features in preferred embodiments of the inventiondescried below, the device further comprises a voltage source forgenerating electrostatic force between the first and the second tubularnanostructures, thereby to close or open the first and the secondtubular nanostructures on the nanoscale object.

According to yet a further aspect of the present invention there isprovided an electronic switching or amplifying device comprising asource electrode, a drain electrode, a gate electrode and a channel,wherein at least one of the gate electrode and the channel comprises ananostructure being composed of a plurality of peptides each includingno more than 4 amino acids, wherein at least one of the 4 amino acids isan aromatic amino acid.

According to still a further aspect of the present invention there isprovided an electronic inverter having a first switching device and asecond switching device, each of the first switching device and thefirst switching device comprising a source electrode, a drain electrode,a gate electrode and a channel, such that the a drain electrode of thefirst switching device is electrically communicating with the sourceelectrode of the second switching device, wherein at least one of thegate electrode and the channel comprises a nanostructure being composedof a plurality of peptides each including no more than 4 amino acids,wherein at least one of the 4 amino acids is an aromatic amino acid.

According to still further features in the described preferredembodiments the source electrode and the drain electrode are formed on asubstrate.

According to still further features in the described preferredembodiments the substrate comprises a thermal oxide deposited over asilicon substrate.

According to still a further aspect of the present invention there isprovided a composition, comprising a polymer and a nanostructure, thenanostructure being composed of a plurality of peptides, each includingno more than 4 amino acids, wherein at least one of the 4 amino acids isan aromatic amino acid.

According to still a further aspect of the present invention there isprovided a composition, comprising a matrix and a plurality ofnanostructures dispersed throughout the matrix, the nanostructure beingcomposed of a plurality of peptides, each including no more than 4 aminoacids, wherein at least one of the 4 amino acids is an aromatic aminoacid.

According to further features in preferred embodiments of the inventiondescried below, the matrix is selected from the group consisting of ametal matrix, a ceramic matrix and a polymeric matrix.

According to still further features in the described preferredembodiments the matrix is a two-dimensional matrix.

According to still further features in the described preferredembodiments the matrix is a three-dimensional matrix.

According to still a further aspect of the present invention there isprovided a nanofluid comprising nanostructures suspended in a fluid,wherein at least a portion of the nanostructures is composed of aplurality of peptides, each including no more than 4 amino acids,wherein at least one of the 4 amino acids is an aromatic amino acid.

According to still a further aspect of the present invention there isprovided a heat transfer device, comprising a nanofluid and a channelfor holding the nanofluid, the nanofluid comprising nanostructuressuspended in a fluid, wherein at least a portion of the nanostructuresis composed of a plurality of peptides, each including no more than 4amino acids, wherein at least one of the 4 amino acids is an aromaticamino acid, the nanofluid and the channel being designed and constructedsuch that heat is carried by the nanostructures from a first end of thechannel to a second end thereof.

According to further features in preferred embodiments of the inventiondescried below, the heat transfer device further comprises a locomotionsystem for generating locomotion of the nanofluid within the channel.

According to still a further aspect of the present invention there isprovided a method of emitting electrons, the method forming an electricfield near a nanostructure being composed of a plurality of peptides,such that electrons are emitted therefrom, wherein each of the pluralityof peptides of the nanostructure includes no more than 4 amino acids andwherein at least one of the 4 amino acids is an aromatic amino acid.

According to still a further aspect of the present invention there isprovided a method of obtaining information from a nanoscale environment,the method comprising: (a) collecting signals from the nanoscaleenvironment using a nanostructure, the nanostructure being composed of aplurality of peptides each including no more than 4 amino acids, whereinat least one of the 4 amino acids is an aromatic amino acid; and (b)receiving the signals from the nanostructure, thus obtaining informationfrom the nanoscale environment.

According to further features in preferred embodiments of the inventiondescribed below, the method further comprising physically scanning thenanoscale environment using the nanostructure.

According to still further features in the described preferredembodiments the information signals are selected from the groupconsisting of mechanical signals, optical signals, electrical signals,magnetic signals, and chemical signals.

According to still further features in the described preferredembodiments the information signals comprise near field light from thenanoscale environment.

According to still further features in the described preferredembodiments the method further comprises converting physical motion ofthe nanostructure to electric signals.

According to still a further aspect of the present invention there isprovided a method of electron emission lithography, the methodcomprising: (a) using an electron emission source for emittingelectrons, the electron emission source including at least onenanostructure being composed of a plurality of peptides each includingno more than 4 amino acids, wherein at least one of the 4 amino acids isan aromatic amino acid; and (b) collecting the electrons on anelectrically conducting mounting device, thereby performing alithography process on a sample mounted on the mounting device.

According to still further features in the described preferredembodiments the method further comprises generating a magnetic field tothereby direct the electrons to a predetermined location on the sample.

According to still a further aspect of the present invention there isprovided a method of recording binary information, the binaryinformation being composed of a first type of datum and a second type ofdatum, the method comprising using a plurality of nanostructure eachcapable of assuming one of two states, wherein a first state of the twostates correspond to the first type of datum and the second state of thetwo states correspond to the second type of datum; wherein each of theplurality of nanostructures is composed of a plurality of peptides eachincluding no more than 4 amino acids at least one of which being anaromatic amino acid.

According to still a further aspect of the present invention there isprovided a method of transmitting mechanical motion, the methodcomprising: (a) providing a first nanostructure and a secondnanostructure, at least one of the first and the second nanostructuresis composed of a plurality of peptides each includes no more than 4amino acids, wherein at least one of the 4 amino acids is an aromaticamino acid; and (b) generating a motion of the first nanostructure suchthat the motion of the first nanostructure generates a motion of thesecond nanostructure.

According to still a further aspect of the present invention there isprovided a method of grabbing and/or manipulating nanoscale objects, themethod comprising: (a) providing at least one nanostructure composed ofa plurality of peptides each including no more than 4 amino acids,wherein at least one of the 4 amino acids is an aromatic amino acid; and(b) using the at least one nanostructure for grabbing and/ormanipulating the nanoscale objects.

According to further features in preferred embodiments of the inventiondescribed below, the at least one nanostructure are a first tubularnanostructure and a second tubular nanostructure, the first and thesecond tubular nanostructures being capable of at least a constrainedmotion.

According to still further features in the described preferredembodiments the method further comprises generating electrostatic forcebetween the first and the second tubular nanostructures, thereby closingor opening the first and the second tubular nanostructures on thenanoscale object.

According to still a further aspect of the present invention there isprovided a method of transferring heat, the method comprising: (a)providing a channel filled with a nanofluid comprising nanostructuressuspended in a fluid, wherein at least a portion of the nanostructuresis composed of a plurality of peptides, each including no more than 4amino acids, wherein at least one of the 4 amino acids is an aromaticamino acid; and (b) placing the channel in proximity to a heat sourcesuch that the nanofluid transfers heat from a first end of the channelto a second end thereof.

According to further features in preferred embodiments of the inventiondescribed below, the channel is selected from the group consisting of amicrochannel and a nanochannel.

According to still further features in the described preferredembodiments the method further comprises generating locomotion of thenanofluid within the channel.

According to still further features in the described preferredembodiments the nanostructures are selected from the group consisting ofspherical nanostructures and tubular nanostructures.

According to still further features in the described preferredembodiments the nanostructure is coated by a conductive material.

According to still a further aspect of the present invention there isprovided a composition comprising: (i) a tubular, spherical or planarnanostructure being composed of a plurality of peptides, wherein each ofthe plurality of peptides includes no more than 4 amino acids andwhereas at least one of the 4 amino acids is an aromatic amino acid; and(ii) an agent being attached to the tubular, spherical or planarnanostructure.

According to further features in preferred embodiments of the inventiondescribed below, the agent is a drug.

According to still further features in the described preferredembodiments the agent is a nucleic acid molecule.

According to still further features in the described preferredembodiments the agent is a polypeptide.

According to still further features in the described preferredembodiments the agent is capable of being slowly released from thenanostructure.

According to still further features in the described preferredembodiments the nanostructure does not exceed 500 nm in diameter.

According to still further features in the described preferredembodiments the tubular nanostructure is at least 1 nm in length.

According to still a further aspect of the present invention there isprovided a composition for modulated delivery of a chemical to apredetermined location, the composition comprising: a plurality ofnanoshells, the nanoshells having a nanostructure core and a conductiveshell and being capable of converting incident radiation into heatenergy, the nanostructure core is composed of a plurality of peptides,each including no more than 4 amino acids, wherein at least one of the 4amino acids is an aromatic amino acid; and a medium comprising thechemical and a thermally responsive material in thermal contact with thenanoshells.

According to still a further aspect of the present invention there isprovided a method for inducing localized hyperthermia in a cell ortissue of an individual, the method comprising: delivering a pluralityof nanoshells, each having a nanostructure core and a conductive shelland being capable of converting incident radiation into heat energy, thenanostructure core is composed of a plurality of peptides, eachincluding no more than 4 amino acids, wherein at least one of the 4amino acids is an aromatic amino acid; and exposing the nanoshells tothe incident radiation to thereby convert the incident radiation intothe heat energy.

According to further features in preferred embodiments of the inventiondescribed below, the conductive shell is a metal shell.

According to further features in preferred embodiments of the inventiondescribed below, the incident radiation is selected from the groupconsisting of an electromagnetic wave, an electric field, a magneticfield and an ultrasound wave.

According to still further features in the described preferredembodiments the nanoshells comprise an affinity component havingaffinity to the cell or the tissue.

According to still further features in the described preferredembodiments the affinity component comprises a moiety selected from thegroup consisting of an antibody, an antigen, a ligand and a substrate.

According to still further features in the described preferredembodiments each of the 4 amino acids is independently selected from thegroup of naturally occurring amino acids, synthetic amino acids, β-aminoacids, Peptide Nucleic Acid (PNA) and combinations thereof.

According to still further features in the described preferredembodiments at least one of the 4 amino acids is a D-amino acid.

According to still further features in the described preferredembodiments at least one of the 4 amino acids is an L-amino acid.

According to still further features in the described preferredembodiments at least one of the peptide nanostructures comprises atleast two aromatic moieties.

According to still further features in the described preferredembodiments at least one of the peptide nanostructures is ahomodipeptide. According to still further features in the describedpreferred embodiments each of the amino acids is the homodipeptidecomprises an aromatic moiety, such as, but not limited to, substitutednaphthalenyl, unsubstituted naphthalenyl, substituted phenyl orunsubstituted phenyl.

According to still further features in the described preferredembodiments the substituted phenyl is selected from the group consistingof pentafluoro phenyl, iodophenyl, biphenyl and nitrophenyl.

Thus, representative examples of the amino acids in the homopeptideinclude, without limitation, naphthylalanine, p-nitro-phenylalanine,iodo-phenylalanine and fluro-phenylalanine.

According to still further features in the described preferredembodiments the homodipeptide is selected from the group consisting ofnaphthylalanine-naphthylalanine dipeptide (SEQ ID NO: 9),(pentafluro-phenylalanine)-(pentafluro-phenylalanine)dipeptide (SEQ IDNO: 10), (iodo-phenylalanine)-(iodo-phenylalanine)dipeptide (SEQ ID NO:11), (4-phenyl phenylalanine)-(4-phenyl phenylalanine) (SEQ ID NO: 12)dipeptide and (p-nitro-phenylalanine)-(p-nitro-phenylalanine)dipeptide(SEQ ID NO: 13).

According to still further features in the described preferredembodiments the nanostructure is stable at a temperature range of 4-400°C.

According to still further features in the described preferredembodiments the nanostructure is stable in an acidic environment.

According to still further features in the described preferredembodiments the nanostructure is stable in a basic environment.

According to still further features in the described preferredembodiments the nanostructure is coated by a conductive material.

According to still further features in the described preferredembodiments the nanostructure does not exceed 500 nm in diameter.

According to still further features in the described preferredembodiments the nanostructure is at least 1 nm in length.

According to still further features in the described preferredembodiments the nanostructure is biodegradable.

According to still a further aspect of the present invention there isprovided a nanostructure composed of a plurality of polyaromaticpeptides.

According to still further features in the described preferredembodiments the polyaromatic peptides are selected from the groupconsisting of polyphenylalanine peptides, polytriptophane peptides,polytyrosine peptides, non-natural derivatives thereof and combinationsthereof.

According to still further features in the described preferredembodiments the polyaromatic peptides are at least 30 amino acids inlength.

The present invention successfully addresses the shortcomings of thepresently known configurations by providing a novel peptidenanostructure which can be used in numerous mechanical, electronically,chemical, optical and biotechnological applications.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present invention, suitable methods andmaterials are described below. In case of conflict, the patentspecification, including definitions, will control. In addition, thematerials, methods, and examples are illustrative only and not intendedto be limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

In the drawings:

FIG. 1 is a schematic illustration of a device for obtaining informationfrom a nanoscale environment, according to a preferred embodiment of thepresent invention.

FIG. 2 a is a schematic illustration of a field emitter device,according to a preferred embodiment of the present invention.

FIG. 2 b is a schematic illustration of a matrix of row and columnelectrodes, according to a preferred embodiment of the presentinvention.

FIG. 3 is a schematic illustration of an apparatus for electron emissionlithography, according to a preferred embodiment of the presentinvention.

FIGS. 4 a-b are schematic illustration of a memory cell, according to apreferred embodiment of the present invention.

FIG. 5 a is a schematic illustration of an electronic device forswitching, inverting or amplifying, according to a preferred embodimentof the present invention.

FIG. 5 b is a schematic illustration of an inverter, which is formedfrom two devices, each similar to the device of FIG. 5 a, according to apreferred embodiment of the present invention.

FIG. 6 is a schematic illustration of a mechanical transmission device,according to a preferred embodiment of the present invention.

FIG. 7 is a schematic illustration of a nanoscale mechanical device forgriping and/or manipulating objects of nanometric size, according to apreferred embodiment of the present invention.

FIG. 8 is a schematic illustration of a heat transfer device, accordingto a preferred embodiment of the present invention.

FIGS. 9 a-e are photomicrographs depicting the ability ofdiphenylalanine peptides to form nanotubes. FIG. 9 a is a schematicillustration showing the central aromatic core structure of theβ-amyloid polypeptide which is involved in the formation of amyloidfibrils. FIG. 9 b is a photomicrograph showing the assembly ofdiphenylalanine peptides into nanostructures as determined byTransmission Electron Microscopy. FIG. 9 c is a pholomicrograph showinga single nanotubes as visualized by electron microscopy. FIG. 9 d is agraph showing Fourier-transformed infrared spectral analysis of thenanostructures. FIG. 9 e is a photomicrograph showing green-goldbirefringence of Congo-red stained structures visualized between crosspolarizers.

FIGS. 10 a-b are photomicrographs depicting self-assembly ofwell-ordered and elongated peptide nanotubes by a molecular recognitionmotif derived from the β-amyloid polypeptide. FIG. 10 a is a TEM imageof the negatively-stained nanotubes formed by the diphenylalaninepeptide. FIG. 10 b is an HR-TEM image of negatively-stained peptidenanotubes.

FIGS. 11 a-b are SEM images depicting the tubular nanoparticles. FIG. 11a is a Low magnification SEM image of a field of discrete nanotubesexisted as individual entities. The scale bar represents 1 μm. FIG. 11 bis a high magnification SEM image of an individual nanotube. The scalebar represents 200 nm.

FIG. 11 c is a graph showing a statistical distribution of the size ofthe nanotubes.

FIGS. 12 a-b are photomicrographs depicting the formation of peptidenanotubes by different aromatic peptide. FIG. 12 a is a TEM image ofstable nanotubes formed by the self-assembly of D-amino acid buildingblock analogue. FIG. 12 b is a TEM image of a tubular structure formedby the NH2-Phe-Trp-COOH dipeptide (SEQ ID NO: 5). Note, the amorphousaggregates at the background of the image.

FIGS. 13 a-c are photomicrographs showing the ability of aromaticpeptides to form nanotubes as determined by TEM analysis and negativestaining. All peptides were dissolved in HFIP and added to doubledistilled water at a final concentration of 2 mg/ml. Then a 10 μlaliquot of 1 day-aged solution of peptide was placed on 400 mesh coppergrid. Following 1 minute, excess fluid was removed. In negative stainingexperiments, the grid was stained with 2% uranyl acetate in water andafter two minutes excess fluid was removed from the grid. FIG. 13a—NH2-Trp-Trp-COOH (SEQ ID NO: 2); FIG. 13 b—NH2-Trp-Tyr-COOH (SEQ IDNO: 3); FIG. 13 c—NH2-Trp-Phe-COOH (SEQ ID NO: 4).

FIG. 14 is a schematic illustration of a proposed assembly mechanism forthe formation of peptide nanotubes. A stacking interaction betweenaromatic moieties of the peptides is suggested to provide energeticcontribution as well as order and directionality for the initialinteraction. The spectroscopic evidence of β-sheet conformation of thesingle amide bond is reflected by an extension of the amino-acidsresidues to opposite sides and the formation of an extended pleatedsheet that is stabilize by hydrogen bonds and aromatic stackinginteractions. The formation of the tubular structures may occur by aclosure of the extended sheet as previously suggested [Matsui andGologan (2000) J. Phys. Chem. B 104:3383].

FIGS. 15 a-d depict self-assembly of spherical nanometric structures bythe aromatic peptide, diphenylglycine. FIG. 15 a is a schematicillustration showing the diphenylalanine motif, the central core of theβ-amyloid polypeptide, which forms discrete well-ordered peptidenanotubes. FIG. 15 b is a schematic illustration showing the simplestaromatic dipeptide, the diphenylglycine peptide. FIG. 15 c is aphotomicrograph depicting Low magnification transmission electronmicroscopy (TEM) image of negatively stained nanospheres formed by thediphenyglycine peptide. FIG. 15 d is a photomicrograph depicting highmagnification TEM image of the negatively stained nanosphere.

FIGS. 16 a-c are photomicrgraphs showing structural properties ofself-assembled nanospheres. FIG. 16 a shows high magnification (X400,000) cold field emission gun (CFEG) high-resolution scanningelectron microscope (HR-SEM) image of the nanospheres formed by thediphenyglycine peptide. FIG. 16 b shows the nanospheres height asanalyzed by atomic force microscopy (AFM) topography. FIG. 16 c is athree-dimensional AFM topography image of the nanospheres.

FIGS. 17 a-b are photomicrographs depicting the stability of thenanostructures at extreme chemical conditions, as observed by TEM.Self-assembled nanospheres were incubated in the presence of strong acidor base FIG. 17 a shows the nanospheres following 5 hours of incubationin the presence of 10% TFA. FIG. 17 b shows the nanospheres following 5hours of incubation in the presence of 1M NaOH.

FIGS. 18 a-d are photomicrographs showing the formation of nanospheresby peptides which include a thiol group. FIG. 18 a is a schematicpresentation of the Cys-Phe-Phe (CFF) tripeptide. FIG. 18 b is aphotomicrograph showing low magnification TEM microphage of thenanospheres formed by the CFF peptide. FIG. 18 c is a photomicrographshowing high magnification TEM microphage of the nanospheres formed bythe CFF peptide. FIG. 18 d is a schematic presentation of the chemicalreaction that modifies an amine to a thiol in the context of thediphenylalanine peptide. FIG. 18 e is a photomicrograph showing lowmagnification TEM microphage of the nanotubes formed by the FF peptide.FIG. 18 b is a photomicrograph showing low magnification TEM microphageof the nanospheres formed by FF peptide that self-assembled in thepresence of 2-iminothiolane.

FIGS. 19 a-c shows the self-assembly of tubular nanometric structures bypolyphenylalanine peptides. FIG. 19 a is a scanning electron microscopy(SEM) image showing the nanotubes formed by the polyphenylalaninepeptide. FIG. 19 b is a photomicrograph showing Congo Red staining of 1day aged solution of polyphenylalanine peptide nanotubes. FIG. 19 c is agraph showing the secondary structure of polyphenylalanine nanotubes asdetermined by Fourier transform infrared spectroscopy.

FIG. 20 is a schematic illustration of a chemical structure of anaphthylalanine-naphthylalanine (Nal-Nal) dipeptide.

FIG. 21 is an electron microscope image of Nal-Nal tubularnanostructures.

FIGS. 22A-D are electron microscope images of tubular and planarnanostructures assembled from the following aromatic-homodipeptides:(pentafluro-phenylalanine)-(pentafluro-phenylalanine) (FIG. 22A),(iodo-phenylalanine)-(iodo-phenylalanine) (FIG. 22B), (4-phenylphenylalanine)-(4-phenyl phenylalanine) (FIG. 22C), and(p-nitro-phenylalanine)-(p-nitro-phenylalanine) (FIG. 22D).

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is of a peptide nanostructures and methods ofgenerating same, which can be used in numerous applications.Specifically, the present invention can be used in numerousapplications, such as, but not limited to, transistors, field emitters,display devices, memory chips, cooling systems and nano-mechanicaldevices.

The principles and operation of the present invention may be betterunderstood with reference to the drawings and accompanying descriptions.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details set forth in the following description or exemplified bythe Examples. The invention is capable of other embodiments or of beingpracticed or carried out in various ways. Also, it is to be understoodthat the phraseology and terminology employed herein is for the purposeof description and should not be regarded as limiting.

Self-assembled nanostructures allow controlled fabrication of novelnanoscopic materials and devices. Nanotubular structures areparticularly important structural elements as they may serve in numerousapplications, for example, as nanowires and nanoscaffolds. Most widelyused nanotubes are made of carbon or peptide assemblers (i.e., buildingblocks). While carbon nanotubes, suffer from major structural defectsincluding branching and bending resulting in spatial structures withunpredictable electronic, molecular and structural properties, peptidenanotubes such as those composed of surfactant like peptides and cyclicD-, L-peptide subunits are formed either as crystals, networks, orbundles of nanostructures.

While reducing the present invention to practice, the present inventoruncovered that aromatic peptides (e.g., diphenylalanine) are capable offorming tubular, spherical and planar nanostructures, which can be usedin numerous mechanical, electrical, chemical, optical andbiotechnological systems.

It will be appreciated that the term nanotubes was previously attributedto the hollow nanometric channels, which are formed within themacroscopic crystal structure of diphenylalanine peptides. However,these entities are not the individual nanostructures formed by thepresent invention, but rather are macrioscopic bundles, which cannot beused as nanotubes [Gorbitz (2001) Chemistry 38:6791].

This discrepancy in results can be explained by the different conditionswhich were used to assemble the structures. While Gorbitz allowedcrystallization by evaporation of an aqueous peptide solution in hightemperature (i.e., 80° C.), the present inventor allowed self-assemblyin an aqueous solution under mild-conditions (see Example 1 of theExamples section which follows).

Thus, according to one aspect of the present invention, there isprovided a tubular, spherical or planar nanostructure. The nanostructureof this aspect of the present invention is composed of a plurality ofpeptides, each peptide including no more than 4 amino acids of which atleast one is an aromatic amino acid.

As used herein the phrase “tubular, spherical or planar nanostructure”refers to a planar (e.g., disk-shape), spherical elongated tubular orconical structure having a diameter or a cross-section of less than 1 μm(preferably less than 500 nm, more preferably less than about 50 nm,even more preferably less than about 5 nm). The length of the tubularnanostructure of the present invention is preferably at least 1 μm, morepreferably at least 10 nm, even more preferably at least 100 nm and evenmore preferably at least 500 nm. It will be appreciated, though, thatthe tubular structure of the present invention can be of infinite length(i.e., macroscopic fibrous structures) and as such can be used in thefabrication of hyper-strong materials.

The nanostructure of the present invention is preferably hollow,conductive or semi-conductive.

According to a preferred embodiment of this aspect of the presentinvention the peptide is a dipeptide or a tripeptide such as set forthin SEQ ID NO: 1, 5, 6, 7 or 8 (see the Examples section which follows).Depending on the rigidity of the molecular structure of the peptideused, tubular, spherical or planar nanostructures are formed. Thus, forexample a plurality of diphenylglycine peptides which offer similarmolecular properties as diphenylalenine peptides albeit with a lowerdegree of rotational freedom around the additional C—C bond and a highersteric hindrence will self-assemble into nano spheres, while a pluralityof diphenylalenine peptides will self-assemble into nanotubes.

The present invention also envisages nanostructures which are composedof a plurality of polyaromatic peptides being longer than the abovedescribed (e.g., 50-136 amino acids).

As used herein the phrase “polyaromatic peptides” refers to peptideswhich include at least 80%, at least 85% at least 90%, at least 95% ormore, say 100% aromatic amino acid residues. These peptides can behomogenic (e.g., polyphenylalanine, see Example 3 of the Examplessection which follows) or heterogenic of at least 10, at least 15, atleast 20, at least 25, at least 30, at least 35, at least 40, at least45, at least 50, at least 55, at least 60, at least 65, at least 70, atleast 75, at least 80, at least 85, at least 90, at least 95, at least100, at least 105, at least 110, at least 120, at least 125, at least130, at least 135, at least 140, at least 145, at least 150, at least155, at least 160, at least 170, at least 190, at least 200, at least300, at least 500 amino acids.

The term “peptide” as used herein encompasses native peptides (eitherdegradation products, synthetically synthesized peptides or recombinantpeptides) and peptidomimetics (typically, synthetically synthesizedpeptides), as well as peptoids and semipeptoids which are peptideanalogs, which may have, for example, modifications rendering thepeptides more stable while in a body or more capable of penetrating intocells. Such modifications include, but are not limited to N terminusmodification, C terminus modification, peptide bond modification,including, but not limited to, CH2-NH, CH2-S, CH2-S═O, O═C—NH, CH2-O,CH2-CH2, S═C—NH, CH═CH or CF═CH, backbone modifications, and residuemodification. Methods for preparing peptidomimetic compounds are wellknown in the art and are specified, for example, in Quantitative DrugDesign, C. A. Ramsden Gd., Chapter 17.2, F. Choplin Pergamon Press(1992), which is incorporated by reference as if fully set forth herein.Further details in this respect are provided hereinunder.

Peptide bonds (—CO—NH—) within the peptide may be substituted, forexample, by N-methylated bonds (—N(CH3)-CO—), ester bonds(—C(R)H—C—O—O—C(R)—N—), ketomethylen bonds (—CO—CH2-), α-aza bonds(—NH—N(R)—CO—), wherein R is any alkyl, e.g., methyl, carba bonds(—CH2-NH—), hydroxyethylene bonds (—CH(OH)—CH2-), thioamide bonds(—CS—NH—), olefinic double bonds (—CH═CH—), retro amide bonds (—NH—CO—),peptide derivatives (—N(R)—CH2-CO—), wherein R is the “normal” sidechain, naturally presented on the carbon atom.

These modifications can occur at any of the bonds along the peptidechain and even at several (2-3) at the same time.

Natural aromatic amino acids, Trp, Tyr and Phe, may be substituted forsynthetic non-natural acid such as Phenylglycine, TIC, naphthylalanine(Nal), ring-methylated derivatives of Phe, halogenated derivatives ofPhe or O-methyl-Tyr, and β amino-acids.

In addition to the above, the peptides of the present invention may alsoinclude one or more modified amino acids (e.g., thiolated amino acids,see Example 2 of the Examples section, or biotinylated amino acids) orone or more non-amino acid monomers (e.g. fatty acids, complexcarbohydrates etc). Also contemplated are homodipeptides, and morepreferably aromatic homodipeptides in which each of the amino acidscomprises an aromatic moiety, such as, but not limited to, substitutedor unsubstituted naphthalenyl and substituted or unsubstituted phenyl.The aromatic moiety can alternatively be substituted or unsubstitutedheteroaryl such as, for example, indole, thiophene, imidazole, oxazole,thiazole, pyrazole, pyridine, pyrimidine, quinoline, isoquinoline,quinazoline, quinoxaline, and purine

When substituted, the phenyl, naphthalenyl or any other aromatic moietyincludes one or more substituents such as, but not limited to, alkyl,trihaloalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl,heteroalicyclic, halo, nitro, azo, hydroxy, alkoxy, thiohydroxy,thioalkoxy, cyano, and amine.

As used herein, the term “alkyl” refers to a saturated aliphatichydrocarbon including straight chain and branched chain groups.Preferably, the alkyl group has 1 to 20 carbon atoms. The alkyl groupmay be substituted or unsubstituted. When substituted, the substituentgroup can be, for example, trihaloalkyl, alkenyl, alkynyl, cycloalkyl,aryl, heteroaryl, heteroalicyclic, halo, nitro, azo, hydroxy, alkoxy,thiohydroxy, thioalkoxy, cyano, and amine.

A “cycloalkyl” group refers to an all-carbon monocyclic or fused ring(i.e., rings which share an adjacent pair of carbon atoms) group whereinone of more of the rings does not have a completely conjugatedpi-electron system. Examples, without limitation, of cycloalkyl groupsare cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexane,cyclohexadiene, cycloheptane, cycloheptatriene, and adamantane. Acycloalkyl group may be substituted or unsubstituted. When substituted,the substituent group can be, for example, alkyl, trihaloalkyl, alkenyl,alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, nitro,azo, hydroxy, alkoxy, thiohydroxy, thioalkoxy, cyano, and amine.

An “alkenyl” group refers to an alkyl group which consists of at leasttwo carbon atoms and at least one carbon-carbon double bond.

An “alkynyl” group refers to an alkyl group which consists of at leasttwo carbon atoms and at least one carbon-carbon triple bond.

An “aryl” group refers to an all-carbon monocyclic or fused-ringpolycyclic (i.e., rings which share adjacent pairs of carbon atoms)groups having a completely conjugated pi-electron system. Examples,without limitation, of aryl groups are phenyl, naphthalenyl andanthracenyl. The aryl group may be substituted or unsubstituted. Whensubstituted, the substituent group can be, for example, alkyl,trihaloalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl,heteroalicyclic, halo, nitro, azo, hydroxy, alkoxy, thiohydroxy,thioalkoxy, cyano, and amine.

A “heteroaryl” group refers to a monocyclic or fused ring (i.e., ringswhich share an adjacent pair of atoms) group having in the ring(s) oneor more atoms, such as, for example, nitrogen, oxygen and sulfur and, inaddition, having a completely conjugated pi-electron system. Examples,without limitation, of heteroaryl groups include pyrrole, furane,thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrimidine,quinoline, isoquinoline and purine. The heteroaryl group may besubstituted or unsubstituted. When substituted, the substituent groupcan be, for example, alkyl, trihaloalkyl, alkenyl, alkynyl, cycloalkyl,aryl, heteroaryl, heteroalicyclic, halo, nitro, azo, hydroxy, alkoxy,thiohydroxy, thioalkoxy, cyano, and amine.

A “heteroalicyclic” group refers to a monocyclic or fused ring grouphaving in the ring(s) one or more atoms such as nitrogen, oxygen andsulfur. The rings may also have one or more double bonds. However, therings do not have a completely conjugated pi-electron system. Theheteroalicyclic may be substituted or unsubstituted. When substituted,the substituted group can be, for example, lone pair electrons, alkyl,trihaloalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl,heteroalicyclic, halo, nitro, azo, hydroxy, alkoxy, thiohydroxy,thioalkoxy, cyano, and amine. Representative examples are piperidine,piperazine, tetrahydro furane, tetrahydropyrane, morpholino and thelike.

A “hydroxy” group refers to an —OH group.

An “azide” group refers to a —N═N≡N group.

An “alkoxy” group refers to both an —O-alkyl and an —O-cycloalkyl group,as defined herein.

An “aryloxy” group refers to both an —O-aryl and an —O-heteroaryl group,as defined herein.

A “thiohydroxy” group refers to an —SH group.

A “thioalkoxy” group refers to both an —S-alkyl group, and an—S-cycloalkyl group, as defined herein.

A “thioaryloxy” group refers to both an —S-aryl and an —S-heteroarylgroup, as defined herein.

A “halo” group refers to fluorine, chlorine, bromine or iodine.

A “trihaloalkyl” group refers to an alkyl substituted by three halogroups, as defined herein. A representative example is trihalomethyl.

An “amino” group refers to an —NR′R″ group where R′ and R″ are hydrogen,alkyl, cycloalkyl or aryl.

A “nitro” group refers to an —NO₂ group.

A “cyano” group refers to a —C≡N group.

Representative examples of such homodipeptides include, withoutlimitation, a naphthylalanine-naphthylalanine (Nal-Nal) dipeptides,(pentafluro-phenylalanine)-(pentafluro-phenylalanine),(iodo-phenylalanine)-(iodo-phenylalanine), (4-phenylphenylalanine)-(4-phenyl phenylalanine) and(p-nitro-phenylalanine)-(p-nitro-phenylalanine) (see Example 4-5 andFIGS. 20-22).

As used herein in the specification and in the claims section below theterm “amino acid” or “amino acids” is understood to include the 20naturally occurring amino acids; those amino acids often modifiedpost-translationally in vivo, including, for example, hydroxyproline,phosphoserine and phosphothreonine; and other unusual amino acidsincluding, but not limited to, 2-aminoadipic acid, hydroxylysine,isodesmosine, nor-valine, nor-leucine and omithine. Furthermore, theterm “amino acid” includes both D- and L-amino acids.

Tables 1 and 2 below list naturally occurring amino acids (Table 1) andnon-conventional or modified amino acids (Table 2) which can be usedwith the present invention. TABLE 1 Three-Letter Amino Acid AbbreviationOne-letter Symbol alanine Ala A Arginine Arg R Asparagine Asn N Asparticacid Asp D Cysteine Cys C Glutamine Gln Q Glutamic Acid Glu E glycineGly G Histidine His H isoleucine Iie I leucine Leu L Lysine Lys KMethionine Met M phenylalanine Phe F Proline Pro P Serine Ser SThreonine Thr T tryptophan Trp W tyrosine Tyr Y Valine Val V Any aminoacid as above Xaa X

TABLE 2 Non-conventional amino acid Code Non-conventional amino acidCode α-aminobutyric acid Abu L-N-methylalanine Nmalaα-amino-α-methylbutyrate Mgabu L-N-methylarginine Nmargaminocyclopropane-carboxylate Cpro L-N-methylasparagine Nmasnaminoisobutyric acid Aib L-N-methylaspartic acid Nmaspaminonorbornyl-carboxylate Norb L-N-methylcysteine Nmcyscyclohexylalanine Chexa L-N-methylglutamine Nmgin cyclopentylalanineCpen L-N-methylglutamic acid Nmglu D-alanine Dal L-N-methylhistidineNmhis D-arginine Darg L-N-methylisolleucine Nmile D-aspartic acid DaspL-N-methylleucine Nmleu D-cysteine Dcys L-N-methyllysine NmlysD-glutamine Dgln L-N-methylmethionine Nmmet D-glutamic acid DgluL-N-methylnorleucine Nmnle D-histidine Dhis L-N-methylnorvaline NmnvaD-isoleucine Dile L-N-methylornithine Nmorn D-leucine DleuL-N-methylphenylalanine Nmphe D-lysine Dlys L-N-methylproline NmproD-methionine Dmet L-N-methylserine Nmser D-ornithine DornL-N-methylthreonine Nmthr D-phenylalanine Dphe L-N-methyltryptophanNmtrp D-proline Dpro L-N-methyltyrosine Nmtyr D-serine DserL-N-methylvaline Nmval D-threonine Dthr L-N-methylethylglycine NmetgD-tryptophan Dtrp L-N-methyl-t-butylglycine Nmtbug D-tyrosine DtyrL-norleucine Nle D-valine Dval L-norvaline Nva D-α-methylalanine Dmalaα-methyl-aminoisobutyrate Maib D-α-methylarginine Dmargα-methyl-γ-aminobutyrate Mgabu D-α-methylasparagine Dmasnα-methylcyclohexylalanine Mchexa D-α-methylaspartate Dmaspα-methylcyclopentylalanine Mcpen D-α-methylcysteine Dmcysα-methyl-α-napthylalanine Manap D-α-methylglutamine Dmglnα-methylpenicillamine Mpen D-α-methylhistidine DmhisN-(4-aminobutyl)glycine Nglu D-α-methylisoleucine DmileN-(2-aminoethyl)glycine Naeg D-α-methylleucine DmleuN-(3-aminopropyl)glycine Norn D-α-methyllysine DmlysN-amino-α-methylbutyrate Nmaabu D-α-methylmethionine Dmmetα-napthylalanine Anap D-α-methylornithine Dmorn N-benzylglycine NpheD-α-methylphenylalanine Dmphe N-(2-carbamylethyl)glycine NglnD-α-methylproline Dmpro N-(carbamylmethyl)glycine Nasn D-α-methylserineDmser N-(2-carboxyethyl)glycine Nglu D-α-methylthreonine DmthrN-(carboxymethyl)glycine Nasp D-α-methyltryptophan DmtrpN-cyclobutylglycine Ncbut D-α-methyltyrosine Dmty N-cycloheptylglycineNchep D-α-methylvaline Dmval N-cyclohexylglycine Nchex D-α-methylalnineDnmala N-cyclodecylglycine Ncdec D-α-methylarginine DnmargN-cyclododeclglycine Ncdod D-α-methylasparagine DnmasnN-cyclooctylglycine Ncoct D-α-methylasparatate DnmaspN-cyclopropylglycine Ncpro D-α-methylcysteine DnmcysN-cycloundecylglycine Ncund D-N-methylleucine DnmleuN-(2,2-diphenylethyl)glycine Nbhm D-N-methyllysine DnmlysN-(3,3-diphenylpropyl)glycine Nbhe N-methylcyclohexylalanine NmchexaN-(3-indolylyethyl)glycine Nhtrp D-N-methylornithine DnmornN-methyl-γ-aminobutyrate Nmgabu N-methylglycine NalaD-N-methylmethionine Dnmmet N-methylaminoisobutyrate NmaibN-methylcyclopentylalanine Nmcpen N-(1-methylpropyl)glycine NileD-N-methylphenylalanine Dnmphe N-(2-methylpropyl)glycine NileD-N-methylproline Dnmpro N-(2-methylpropyl)glycine Nleu D-N-methylserineDnmser D-N-methyltryptophan Dnmtrp D-N-methylserine DnmserD-N-methyltyrosine Dnmtyr D-N-methylthreonine Dnmthr D-N-methylvalineDnmval N-(1-methylethyl)glycine Nva γ-aminobutyric acid GabuN-methyla-napthylalanine Nmanap L-t-butylglycine TbugN-methylpenicillamine Nmpen L-ethylglycine EtgN-(p-hydroxyphenyl)glycine Nhtyr L-homophenylalanine HpheN-(thiomethyl)glycine Ncys L-α-methylarginine Marg penicillamine PenL-α-methylaspartate Masp L-α-methylalanine Mala L-α-methylcysteine McysL-α-methylasparagine Masn L-α-methylglutamine MglnL-α-methyl-t-butylglycine Mtbug L-α-methylhistidine MhisL-methylethylglycine Metg L-α-methylisoleucine Mile L-α-methylglutamateMglu D-N-methylglutamine Dnmgln L-α-methylhomo phenylalanine MhpheD-N-methylglutamate Dnmglu N-(2-methylthioethyl)glycine NmetD-N-methylhistidine Dnmhis N-(3-guanidinopropyl)glycine NargD-N-methylisoleucine Dnmile N-(1-hydroxyethyl)glycine NthrD-N-methylleucine Dnmleu N-(hydroxyethyl)glycine Nser D-N-methyllysineDnmlys N-(imidazolylethyl)glycine Nhis N-methylcyclohexylalanine NmchexaN-(3-indolylyethyl)glycine Nhtrp D-N-methylornithine DnmornN-methyl-γ-aminobutyrate Nmgabu N-methylglycine NalaD-N-methylmethionine Dnmmet N-methylaminoisobutyrate NmaibN-methylcyclopentylalanine Nmcpen N-(1-methylpropyl)glycine NileD-N-methylphenylalanine Dnmphe N-(2-methylpropyl)glycine NleuD-N-methylproline Dnmpro D-N-methyltryptophan Dnmtrp D-N-methylserineDnmser D-N-methyltyrosine Dnmtyr D-N-methylthreonine DnmthrD-N-methylvaline Dnmval N-(1-methylethyl)glycine Nval γ-aminobutyricacid Gabu N-methyla-napthylalanine Nmanap L-t-butylglycine TbugN-methylpenicillamine Nmpen L-ethylglycine EtgN-(p-hydroxyphenyl)glycine Nhtyr L-homophenylalanine HpheN-(thiomethyl)glycine Ncys L-α-methylarginine Marg penicillamine PenL-α-methylaspartate Masp L-α-methylalanine Mala L-α-methylcysteine McysL-α-methylasparagine Masn L-α-methylglutamine MglnL-α-methyl-t-butylglycine Mtbug L-α-methylhistidine MhisL-methylethylglycine Metg L-α-methylisoleucine Mile L-α-methylglutamateMglu L-α-methylleucine Mleu L-α-methylhomophenylalanine MhpheL-α-methylmethionine Mmet N-(2-methylthioethyl)glycine NmetL-α-methylnorvaline Mnva L-α-methyllysine Mlys L-α-methylphenylalanineMphe L-α-methylnorleucine Mnle L-α-methylserine mser L-α-methylornithineMorn L-α-methylvaline Mtrp L-α-methylproline Mpro L-α-methylleucine MvalNnbhm L-α-methylthreonine MthrN-(N-(2,2-diphenylethyl)carbamylmethyl-glycine Nnbhm L-α-methyltyrosineMtyr 1-carboxy-1-(2,2-diphenylethylamino)cyclopropane NmbcL-N-methylhomophenylalanine NmhpheN-(N-(3,3-diphenylpropyl)carbamylmethyl(1)glycine Nnbhe

The nanostructures of the present invention are preferably generated byallowing a highly concentrated aqueous solution of the peptides of thepresent invention to self-assemble under mild conditions as detailed inExamples 1 and 2 of the Examples section which follows.

The resulting nanostructures are preferably stable under acidic and/orbasic pH conditions, a wide range of temperatures (e.g., 4-400° C., morepreferably, 4-200° C.) and/or proteolytic conditions (i.e., proteinaseK).

Depending on the number and type of amino acids used, the nanostructurecan be insulators, conductors or semiconductors. The nanostructure ofthe present invention can also be utilized as carriers onto which atomsof different materials (e.g., conductive materials, chemical orbiological agents, etc.) may be incorporated.

A detailed description of the nanostructure generated according to theteachings of the present invention follows below, starting first with adescription of the applications of such nanostructures and theadvantages offered thereby.

The nanostructure of the present invention has numerous potentialapplications. Having a substantially high aspect ratio, thenanostructure of the present invention is an ideal candidate for use inprobing application. For example, a nanostructure having a tip diameterof about 10 nm and a length of several micrometers can be used as thetip of an atomic force microscope to probe deep crevices found onintegrated circuits, biological molecules or any other nanoscaleenvironment.

Additionally, the nanostructure of the present invention has exceptionalmaterial properties. More specifically, due to multiple cooperativeforces (hydrogen bonding and hydrophobic packing), the nanostructure ishighly robust under extreme pH and temperatures. When another material(e.g., a polymer or a ceramic material) is reinforced with thenanostructure of the present invention, the resulting composition ischaracterized by a mechanical strength of one or more order of magnitudeabove the strength of the host material. Such a strong compositematerial is well suited for many applications such as, but not limitedto, in the defense, aerospace and automobile industries.

An additional potential application of the nanostructure of the presentinvention is in the field of micro- and nanoelectronic systems. Thenanostructure can be combined with silicon chips so as to restrictmotion of electrons or holes within a nanoscale region thereby toprovide the system with special electric, optical and/or chemicalcharacteristics. For example, the use of nanostructure as gates in anelectronic device allows operation at low gate voltage and enables theswitching of several individual devices on the same substrate.

As mentioned hereinabove, the nanostructures of the present inventioncan be hollow. Being both of nanometer scale and hollow, thenanostructures can serve for heat conduction, e.g., by mixing thenanostructures with a fluid (e.g., a cooling liquid).

Still another potential applications of the nanostructure of the presentinvention is related to enhancement of electromagnetic fields near ultrasmall metal objects. The physical process of strong field enhancementvery close to metal nanoparticles is a well known phenomenon and hasbeen described in detail in the literature. To this end, see, forexample, R. H. Doremus and P. Rao, J. Mater. Res., 11, 2834,(1996); M.Quinten, Appl. Phys. B 73, 245 (2001) and R. D. Averitt, S. L. Westcottand N. J. Halas, J. Opt. Soc. Am. B 16, 1824 (1999), the contents ofwhich are hereby incorporated by reference. In metal nanoparticles,resonant collective oscillations of conduction electrons, also known asparticle plasmons, are excited by an optical field. The resonancefrequency of a particle plasmons is determined mainly by the dielectricfunction of the metal, the surrounding medium and by the shape of theparticle. Resonance leads to a narrow spectrally selective absorptionand an enhancement of the local field confined on and close to thesurface of the metal particle. The spectral width of absorption andnear-field enhancement depends on the decay time of the particleplasmons. A significant enhancement of the effect of optical fieldincrement may be achieved, by coating the nanostructures of the presentinvention by a conducting shall layer. Nanoparticles having suchstructure are called nanoshells.

The process of coating nanostructures having a dielectric core and toform a conducting shell, is known in the art and is described in, forexample, WO 01/06257 and WO 02/28552, the contents of which are herebyincorporated by reference.

Following are representative examples of applications in which thenanostructure of the present invention is preferably incorporated.

Hence, further in accordance with the present invention there isprovided a device for obtaining information from a nanoscaleenvironment. Broadly speaking, this device is capable of serving as aninterface between macroscopic systems and individual objects havingnanometer dimensions. The device according to this aspect of the presentinvention may comprise one or more nanostructures, which facilitateinformation exchange between the macroscopic system and the nanoscaleenvironment. Individual nanostructures or bundles of nanostructures canbe recovered from peptides, as further detailed hereinabove, inaccordance with the present invention. Assemblies of nanostructures canbe fabricated, for example, by self-assembly of groups ofnanostructures, as further detailed and exemplified in the Examplessection that follows.

Referring now to the drawings, FIG. 1 is a schematic illustration of thedevice described above, which is referred to herein as device 10. In itsmost basic form, device 10 comprises a nanostructure 12 and a detectionsystem 16. As stated, nanostructure 12 preferably comprises a pluralityof peptides, each having no more than 4 amino acids.

Nanostructure 12 serves for collecting signals from a nanoscaleenvironment 14. Any type of signals can be collected by nanostructure 12including, without limitation, mechanical, optical, electrical, magneticand chemical signals. Detection system 16 serves for interfacing withnanostructure 12 and receiving the signals collected thereby. Hence, bycollecting signals using nanostructure 12 and detecting the signalsusing system 16, device 10 is capable of sensing, measuring andanalyzing nanoscale environment 14.

According to a preferred embodiment of the present invention device 10may further comprise a supporting element 18 onto which nanostructure 12is mounted. Nanostructure 12 is connected to supporting element 18 atone end, with the other end being free and, due to its nanometricdimension, capable of coming into direct contact or near proximity tonanoscale environment 14. Preferably, supporting element 18 canphysically scan nanoscale environment 14 to thereby allow nanostructure12 to collect signals from, or deliver signals to a plurality oflocations of nanoscale environment 14. The “sensing end” ofnanostructure 12 interacts with objects being sensed, measured oranalyzed by means which are (either individually or in combination)physical, electrical, chemical, electromagnetic or biological. Thisinteraction produces forces, electrical currents or chemical compoundswhich reveal information about the object.

Nanostructure 12 and supporting element 18 in combination canessentially be considered as a transducer for interacting with nanoscaleenvironment 14. Conventional probe microscopy techniques are enabled andimproved by the use of device 10, according to a preferred embodiment ofthe present invention.

Examples of conventional systems of this type include scanning tunnelingmicroscopes, atomic force microscopes, scanning force microscopes,magnetic force microscopes and magnetic resonance force microscopes.

Device 10 is fundamentally different from conventional probe microscopytips in its shape and its mechanical, electronic, chemical and/orelectromagnetic properties. This difference permits new modes ofoperation of many probe microscopes, and new forms of probe microscopy.Device 10 is capable of imaging, at nanoscale resolution or greater,surfaces and other substrates including individual atoms or moleculessuch as biolmolecules. Device 10 can replace relevant parts (e.g., tips)of any of the above systems.

In a preferred embodiment, supporting element 18 and/or nanostructure 12may be pre-coated with a layer of conductive material in order toproduce a good electrical contact therebetween.

Device 10 is particularly useful when used in tapping mode atomic forcemicroscopy. In this mode, a change in amplitude of an oscillatingcantilever driven near its resonant frequency is monitored asnanostructure 12 taps the surface of nanoscale environment 14. The sharpfrequency response of high-quality cantilevers makes this techniqueexquisitely sensitive. Nanostructure 14 has the advantage that it isboth stiff below a certain threshold force, but is compliant above thatthreshold force. More specifically, below the Euler buckling force,there is no bending of nanostructure 12. The Euler buckling force ofnanostructure 12 is preferably in the one nano-Newton range. Once theEuler bucking force is exceeded, nanostructure 12 bends easily throughlarge amplitudes with little additional force. In addition,nanostructure 12 is extremely gentle when laterally touching an object.

The result is that gentle, reliable atomic force microscopy imaging maybe accomplished in the tapping mode with even extremely stiff,high-resonant frequency cantilevers. In contrast to the hard siliconpyramidal tip of existing systems, which can easily generate impactforces being larger than 100 nano-Newtons per tap, and therefore maysubstantially modify the geometry of soft samples such as large.bio-molecules, nanostructure 12 serves as a compliant probe whichmoderates the impact of each tap on the surface.

An additional advantage of device 10 is its capability to exploreregions of nanoscale environment 14 previously inaccessible to highresolution scanning probes. In this embodiment, nanostructure 12 ispreferably of tubular shape so as to allow nanostructure 12 to penetrateinto deep trenches of environment 14. Due to the above mention specialmechanical characteristics of nanostructure 12 scanning force microscopyimaging of tortuous structures can be achieved without damagingnanostructure 12 or the imaged object.

Device 10 of the present invention can also be utilized to retrieveother types of information from nanoscale environment 14, such as, butnot limited to, information typically obtained via conventional frictionforce microscopy. Friction force microscopy measures the atomic scalefriction of a surface by observing the transverse deflection of acantilever mounted probe tip. The compliance of nanostructure 12 abovethe Euler threshold as described above, provides for a totally newmethod of elastic force microscopy. By calibration of the Euler bucklingforce for nanostructure 12, and making appropriate atomic forcemicroscopy measurements using nanostructure 12, one can obtain directinformation about the elastic properties of the object being imaged.

Device 10 may also be used to perform nanoscale surface topographymeasurement. Motions of supporting element 18 can be calibrated bymeasurement of surfaces having known geometries (e.g., pyrolyticgraphite with surface steps). Once properly calibrated, supportingelement 18 and nanostructure 12 can provide precise measurement of thetopography of surfaces and fabricated elements such as vias and trencheson integrated-circuit elements.

An additional use of device 10 is in mechanical resonance microscopy,which can be facilitated by mechanical resonances in nanostructure 12.These resonances may be utilized as a means of transduction ofinformation about the object being sensed or modified. Such resonances,as will be known by one skilled in the art, can be sensed by optical,piezoelectric, magnetic and/or electronic means.

Nanostructure 12 can also act as a sensitive antenna for electromagneticradiation. The response of nanostructure 12 to electromagnetic radiationmay be recorded by detecting and measuring frequency currents passingtherethrough as it and the object being sensed interact together in anonlinear way with electromagnetic radiation of two or more frequencies.Via its interaction with electromagnetic fields of specifiedfrequencies, nanostructure 12 may excite electronic, atomic, molecularor condensed-matter states in the object being examined, and thetransduction of information about that object may occur by observationof the manifestations of these states.

Also of interest is the use of device 10 for probing biological systems.For example, device 10 can perform DNA sequencing by atomic forcemicroscopy imaging of DNA molecules whereby nanostructure 12, due to itsphysical and chemical properties, permits the recognition of individualbases in the molecule.

In another biological application, device 10 can also be used forelectrical or electrochemical studies of living cells. Knowledge of cellactivity can be achieved, e.g., by measuring and recording electricalpotential changes occurring within a cell. For example, device 10 of thepresent invention can accurately monitor specific cytoplasmic ions andcytosolic calcium concentrations with a spatial resolution far superiorto those presently available. Living cells which can be studied usingdevice 10 include, without limitations, nerve cell bodies and tissueculture cells such as smooth muscle, cardiac, and skeletal muscle cells.

Additionally, device 10 can be used, for example, to obtain and measurenear field light from nanoscale environment 14. For the purpose ofproviding a self contained document a description of the near fieldphenomenon precedes the description of the presently preferredembodiment of the invention.

When light impinges on a boundary surface (such as the surface ofnanoscale environment 14) having a varying refractive index at an anglewhich causes total reflection, the incident light is totally reflectedon the boundary surface (reflection plane), in which case the lightexudes to the opposite side of the reflection plane. This exuding lightis called “near-field light.” Other than the foregoing, the near-fieldlight also includes light which exudes from a miniature aperture smallerthan the wavelength of the light, through which the light is passed.

The near-field light can be utilized to analyze a surface state (shape,characteristics or the like) of a sample such as semiconductormaterials, organic or inorganic materials, vital samples (cells) and thelike. An ordinary optical microscope cannot measure a sample at aresolution higher than the wavelength of light due to diffraction of thelight. This is called “diffraction limit of light.” An analysisutilizing near-field light permits measurements at a resolutionexceeding the diffraction limit of light.

According to a preferred embodiment of the present inventionnanostructure 12 is adapted to collect near-field light of nanoscaleenvironment 14. As the near-field light incidents on nanostructure 12,electronic excitation are induced therein. These electronic excitationscause a current to flow through nanostructure 12, toward detectionsystem 16 which detects, records and/or analyzes the current.

It is appreciated that the above embodiments merely exemplify thepotential use of device 10 for obtaining vital information from ananoscale environment, previously unattained by conventional systems andapparati. The geometrical shape, nanometric size and physical propertiesof nanostructure 12 may also be used also for performing tasks, otherthan, obtaining information.

Nanostructure generated in accordance with the teachings of the presentinvention can also be utilized as part of a field emitting device.

Hence, according to another aspect of the present invention, there isprovided a field emitter device, which is referred to herein as device20.

Reference is now made to FIG. 2 a, which is a schematic illustration ofa cross sectional view of device 20, according to a preferred embodimentof the present invention. Device 20 preferably comprises an electrode 22and a nanostructure 12. Electrode 22 and nanostructure 12 are designedand constructed such that when an electrical field is formedtherebetween, electrons 27 are extracted from nanostructure 12 bytunneling through the surface potential barrier. Once emitted fromnanostructure 12, electrons 27 can be accelerated, redirected andfocused so as to energetically excite atoms of a specific material, asfurther detailed hereinunder.

Device 20 may be integrated in many apparati, such as, but not limitedto, a field emitter display. In this embodiment, a plurality ofnanostructures may be positioned in cross points 28 of a matrix 29 ofelectrodes. Matrix 29, better illustrated in FIG. 2 b, is formed of aplurality of row and column electrodes. Thus, each cross point 28 can beaddressed by signaling the respective row and column electrodes. Upon asuitable signal, addressed to a specific cross point, the respectivebundle of nanostructures 12 emits electrons, in accordance with theabove principle.

Device 20 (or the apparatus in which device 20 is employed) may furthercomprise a substrate 26 having a fluorescent powder coating, capable ofemitting light upon activation by the electrons. The fluorescent powdercoating may be either monochromatic or multichromatic. Multichromaticfluorescent powder may be, for example, such that is capable of emittingred, green and blue light, so that the combination of these colorsprovides the viewer with a color image. Device 20 may further comprise afocusing element 25 for ensuring that electrons 27 strike electrode 22at a predetermined location.

A special use of field emitter device, such as device 20, is in the areaof electron beam lithography, in particular when it is desired toachieve a precise critical dimension of order of a few tens ofnanometers. The present invention successfully provides an apparatus forelectron emission lithography apparatus, generally referred to herein asapparatus 30. As further detailed hereinbelow, apparatus 30 is capableof transferring a pattern of a mask in a nanoscale resolution.

Reference is now made to FIG. 3, which is a schematic illustration ofapparatus 30. Apparatus 30 comprises an electron emission source 32 andan electrically conducting mounting device 34. According to a preferredembodiment of the present invention, sources 32 includes one or morenanostructures 12, which, as stated, is composed of a plurality ofpeptides. Source 32 and mounting device 34 are kept at a potentialdifference, e.g., via a voltage source 36. The potential difference isselected such that electrons are emitted from source 32 (similarly todevice 20).

A sample 38, on which an e-beam resist 39 to be patterned is formed, isdisposed on mounting device 34, in a predetermined distance apart from asource 32. The electrons emitted from nanostructure 12 perform alithography process on a sample 38 mounted thereon. Subsequently, if adeveloping process is performed, portions of resist 39 which wereexposed to the emitted electrons remain when the resist 39 is negative,while portions of resist 39 not exposed to an electron beam remain whenresist 39 is positive.

Source 32 and mounting device 34 are preferably positioned in a magneticfield generated by a magnetic field generator 37. Magnetic fieldgenerator 37 is designed to precisely control a magnetic field accordingto the distance between nanostructures 12 and resist 39, so that theelectrons emitted from nanostructure 12 reach the desired positions onresist 39. Being charged particles moving in a magnetic field, theelectrons are subjected to a magnetic force, perpendicular to theirdirection of motion (and to the direction of the magnetic field vector).Thus, a track of the movement of the electrons is controlled by magneticfield generator 37, which redirect the electron to the desirableposition.

Consequently, the shape of nanostructures 12 can be projected uponsample 38, to thereby perform a lithographic process thereon. Asdescribed above, according to the present invention, sincenanostructures 12 are used as electron emission sources, a lithographyprocess can be performed with a precise critical dimension. In addition,since electrons emitted from nanostructures 12 carbon depreciateportions of resist 39 corresponding to nanostructure 12, a deviationbetween the center of a substrate and the edge thereof are substantiallyprevented.

An additional use of nanostructure 12 is in the field of informationstorage and retrieving.

Reference is now made to FIGS. 4 a-b, which are schematic illustrationof a memory cell, generally referred to herein as cell 40. In itssimplest configuration, cell 40 comprises an electrode 42 and ananostructure 12. Nanostructure 12 preferably capable of assuming one ofat least two states. For example, as already described hereinabove,nanostructure 12 has the capability to deflect when the Euler bucklingforce is exceeded, thus, a first state of nanostructure 12 can be anon-deflected state (when an external force applied on nanostructure isbelow Euler buckling force) and a second state of nanostructure 12 canbe a deflected state (when the external force is above or equals theEuler buckling force).

Nanostructure 12 is preferably be suspended by one or more supports 44over electrode 42. Nanostructure 12 may be held in position onsupport(s) 44 in more than one way. For example, nanostructure 12 isheld in position on support(s) 44 by or any other means, such as, butnot limited to, by anchoring nanostructure 12 to support(s) 44. Theholding of nanostructure 12 in its place on support(s) 44 can also befacilitated by chemical interactions between nanostructure 12 andsupport(s) 44, including, without limitation, covalent bonding.

Electrode 42, nanostructure 12 and the distance therebetween arepreferably selected such that electrical current flows through electrode42 and/or nanostructure 12, generates an electric force on nanostructure12 which is larger than the Euler buckling force. Thus, temporarilyelectric current(s) transform nanostructure 12 from the first state(FIG. 4 a) to the second state (FIG. 4 b).

A plurality of cells like cell 40 can be incorporated to provide anelectromechanical memory array. Each cell in the array can be in eithera first state or a second state thus can store a binary information of afirst type of datum (say, “0”) and a second type of datum (say, “1”). Asthe size of nanostructure 12 is in the nanometric scale, many such cellscan be integrated in a single array so that the information storagecapacity of the entire array is substantially larger, or at leastequivalent to modern memory devices. Each cell may be read or written byapplying currents and or voltages to electrode 42 or nanostructure 12.

More specifically, when nanostructure 12 is in a non-deflected state(FIG. 4 a), cell 40 is characterized by an open circuit, which may besensed as such on either nanostructure 12 or trace electrode 42 when soaddressed. When nanostructure 12 is in a deflected state (FIG. 4 b),cell 40 is characterized by a rectified junction (e.g., Schottky or PN),which may be sensed as such on either nanostructure 12 or traceelectrode 42 when so addressed.

As will be appreciated by one ordinarily skilled in the art, cell 40(and therefore an integrated array of a plurality of such cells) ischaracterized by a high ratio of resistance between “0” and “1” states.Switching between these states is accomplished by the application ofspecific voltages across nanostructure 12. or electrode 42. For example,“readout current” can be applied so that the voltage across a respectivejunction is determined with a “sense amplifier.” It will be appreciatedthat such reads are non-destructive. More specifically, unlike DRAMsystems, where write-back operations are required after each read, cell40 retains its state even once read is performed.

According to another aspect of the present invention, there is providedan electronic device, for switching, inverting or amplifying, generallyreferred to as device 50.

Reference is now made to FIG. 5 a, which is a schematic illustration ofdevice 50. Device 50 comprises a source electrode 52, a drain electrode54, a gate electrode 56 and a channel 58. One or both of gate electrode56 and channel 58 may comprise a nanostructure (e.g., nanostructure 12)which is composed of a plurality of peptides, as further detailedhereinabove. For example, in one embodiment channel 58 is ananostructure and gate electrode 56 is preferably layer of SiO₂ in asilicon wafer.

In its simplest principle, device 50 operates as a transistor. Channel58 has semiconducting properties (either n-type or p-type semiconductingproperties) such that the density of charge carriers can be varied. Avoltage 57 is applied to channel 58 through gate electrode 56, which ispreferably separated from channel 58 by an insulating layer 59. When thevoltage of gate electrode 56 is zero, channel 58 does not contain anyfree charge carriers and is essentially an insulator. As voltage 57 isincreased, the electric field caused thereby attracts electrons (or moregenerally, charge carriers) from source electrode 52 and drain electrode54, so that channel 58 becomes conducting.

Thus, device 50 serves as an amplifier or a switching device where,voltage 57 of gate electrode 56 controls the current flowing from sourceelectrode. 52 and drain electrode 54, when a bias voltage 53 is appliedtherebetween.

Two devices like devices 50 may be combined so as to construct aninverter. Referring to FIG. 5 b, in this embodiment, a first such device(designated 50 a) may include a channel having an n-type semiconductingproperties and a second such device (designated 50 b) may include achannel having an p-type semiconducting properties. Devices 50 a and 50b are preferably connected such that when bias voltage 53 is appliedbetween the source of device 50 a and the drain of device 50 b, thecombined device serves as an inverter between input signal 51 and outputsignal 55.

Following are several aspects of the present invention in whichnanostructure 12 is primarily exploited for performing mechanical tasks.

According to an additional aspect of the present invention, there isprovided a mechanical transmission device, generally referred to hereinas device 60.

Reference is now made to FIG. 6, which is a schematic illustration ofdevice 60, according to a preferred embodiment of the present invention.Device 60 comprises a first nanostructure 12 and a second nanostructure62, which, as stated are composed of a plurality of peptides. First 12and second 62 nanostructures are operatively associated thereamongstsuch that a motion of first nanostructure 12 generates a motion ofsecond nanostructure 62. Both first 12 and second 62 can have any shapesuitable for transmitting motion, such as, but not limited to, atubular, spherical or planar shape. To facilitate the operativeassociation, one or more molecules 64 (e.g., antibodies, ligands, DNA,RNA, or carbohydrates) can be attached to the external surface of first12 and/or second 62 nanostructures.

Hence, device 60 can operate as a nanomachine which could self-repair oradapt to the environment. Preferably, first 12 and/or second 62nanostructures include oppositely charged atoms on their antipodes, sothat an electric field can generate a circular motion. Being of ananometric size, an extremely small magnitude of electric field issufficient for rotating the nanostructures, in an extremely largeangular velocity, typically in the Giga-Hertz range.

Another mechanical application in which nanostructure 12 can be used isillustrated in FIG. 16. In this aspect of the present inventionnanostructure 12 is exploited for the purpose of manipulating nanoscaleobjects. A potential application of the present aspect of the inventionis in the area of assembling nanoelectronic circuit (see, e.g., cell 40or device 50 hereinabove) when nanoscale objects are to be preciselylocated in a predetermined location.

FIG. 16 illustrates a nanoscale mechanical device 70, which comprises atleast one nanostructure 12 designed and configured for grabbing and/ormanipulating a nanoscale object 74. Such operation may be achieved, forexample, using two nanostructures 12, preferably tubular nanostructures,mounted on a mounting device 72, whereby nanostructures 12 perform aconstrained motion to grab object 74.

Mounting device 72 can be, for example, a tip end of an atomic forcemicroscopy cantilever, so that one or both of nanostructures 12 can alsobe utilized as an atomic force microscopy probe. In use, nanostructures12 first scan (e.g., as an atomic force microscopy probe) the regionwhere object 74 is expected, thus confirming the position and shapethereof. This scan me be performed in any method known in the art, suchas, but not limited to, using a three-dimensional driving mechanism 78.

The motion of nanostructure 12 may be controlled, for example, by avoltage source 76 which generates an electrostatic force betweennanostructures 12. Thus, by activating voltage source 76 nanostructures12 can close or open on object 74.

Once nanostructure 12 grip object 74, which, as stated, has been markedby the atomic force microscopy procedure, mounting device 72 can bemoved by three-dimensional driving mechanism 78, to a desired location.Subsequently nanostructures 12 are further opened, thus releasing object74 in its appropriate location. In cases where object 74 fails toseparate from nanostructures 12, e.g., due to Van der Waals forcesbetween object 74 and nanostructures 12, a further voltage can beapplied between nanostructures 12 and the desired location, so thatobject 74 is released by an electrostatic attractive force.

As stated, the nanostructure of the present invention can also be usedfor reinforcing other materials, such as, but not limited to, polymers.Thus, according to yet an additional aspect of the present inventionthere is provided composition, in which a polymer is combined with thenanostructure of the present invention. Preferably, the nanostructure ischemically bonded to or integrated within the polymer chains via one ormore chemical bond types.

Several attachement configurations can be utilized in order to reinforcepolymer chains.

For example, the nanostructure can be linked to one or morechain-terminating group of the polymer chain or to residues of internalpolymer groups. The polymer component of the composition of the presentinvention preferably comprises polymers, including copolymers, which arecapable of chemically bonding with the peptides of the nanostructure, orthose polymers that can be prepared from one or more monomer precursorscapable of bonding with the peptides of the nanostructure either priorto or during polymerization. Representative examples of polymers whichmay be used include without limitation polyethylene glycol (PEG),polysaccharides, DNA, RNA, poly amino-acids, peptide nucleic acid (PNA).

The composition described above, can be used for manufacturing manyforms of articles, such as filaments, carpets, ropes and the like.

A fiber can be formed from the polymer-nanostructure composition bycutting the composition into chips and drying. These chips can then beheated under pressure to bond the chips into a plug. This plug can thenbe heated to a molten state, passed through a mesh screen, and forcedthrough an extrusion orifice. The filament formed by the moltencomposite material can then be pulled away from the orifice and woundonto a bobbin. Such fibers can be incorporated into bulked continuousfilament, and made into carpets, ropes and the like.

Alternatively, the composition describe above can be used as aninjection moldable resin for engineering polymers for use in manyapplications, such as, but not limited to, filters, solenoids and thelike.

The nanostructure of the present invention can also be dispersedthroughout a matrix material to thereby form a free-form structure.Constructing and arranging composite nodal elements to define astructure circumvents the common practice in the industry ofpost-fabrication processing operations. Initially, a structure is oftenfabricated in a mold or by machining and then subjected topost-fabrication processing operations. Post-fabrication processingoperations refer to added steps required beyond initial fabrication sothat the structure exhibits desired dimensions and tolerance. Typically,post-processing operations include for example, among others, machining,cleaning, polishing, grinding, deburring and hole drilling so as toachieve desired dimensions and tolerance of a fabricated structure.

Following is a description of an additional embodiment of the presentinvention in which the nanostructures are used for the purpose ofdelivering energy from one location to the other.

In many industries, there is a great need for more efficient heattransfer fluids. Heat transfer fluids used in today's conventionalthermal systems have inherently poor heat transfer properties. Often,millimeter- or micrometer-sized particles are suspended in heat transferfluids so as to increase the capability of the fluid to deliver heat.The ratio of surface area to volume of the nanostructure of the presentinvention is about three orders of magnitudes larger than that ofmicrometer-sized particles. Since heat transfer occurs on the surface ofa fluid, this feature of the present invention can be used forsignificantly enhancing heat conduction properties of cooling fluids.

Thus, according to a further aspect of the present invention there isprovided, a nanofluid, comprising the nanostructures of the presentinvention suspended in a fluid. The nanofluid of the present inventionis characterized extreme stability and ultra-high thermal conductivity.

The present invention successfully provides a heat transfer device 80which exploits the above mentioned thermal properties of the nanofluid.

Reference is now made to FIG. 8, which is a schematic illustration ofdevice 80. Device 80 comprises a nanofluid 82 and a channel 84 forholding nanofluid 82. As stated, nanofluid 82 comprises nanostructures12 suspended in a fluid 86, where at least a portion of nanostructures12 is composed of a plurality of peptides, as further detailedhereinabove and in accordance with the present invention. Channel 84 ispreferably constructed such that heat is transferred by nanofluid 82,and, in particular, by nanostructure 12, from a first end 87 to a secondend 88 of channel 84.

Channel 84 is preferably in a micrometer size (i.e., a microchannel) ora nanometer size (i.e., a nanochannel), both are known in the art. Inthe embodiment in which channel 84 is a nanochannel, the diameterthereof is larger that the diameter of the largest nanostructure, so asto allow nanofluid 82 to flow freely through channel 84.

Device 80 may further comprise a locomotion system 89 for generatinglocomotion of nanofluid 82 within channel 84. System 89 may operate inany way known in the art for generating locomotion of nanofluid 82. Forexample, in one embodiment, the locomotion of nanofluid 82 can beachieved by an under-pressure formed in channel 84, in which case system89 generates under-pressure. In another embodiment, fluid locomotion canbe achieved by dielectrophoretic forces applied thereon, in which casesystem 89 can be realized, for example, as a mechanism for generating anon-uniform electric field.

Following is a description of additional embodiments of the presentinvention in which the nanostructures described hereinabove are coatedby a conducting shell to form the nanoshell further detailedhereinabove.

Hence, according to yet another aspect of the present invention there isprovided a composition for modulated delivery of a chemical to apredetermined location. The composition comprises a plurality ofnanoshells, each nanoshell having a nanostructure core and a conductiveshell which is capable of converting incident radiation into heatenergy. The nanostructure core is composed of a plurality of peptides,as further detailed hereinabove. The composition further comprises amedium having the chemical and a thermally responsive material (e.g., athermally responsive hydrogels) in thermal contact with the nanoshells.

Composites of thermally responsive hydrogels are known in the art. Forexample, copolymers of N-isopropylacrylamide (NIPAAm) and acrylamide(AAm) exhibit a lower critical solution temperature (LCST) that isslightly above body temperature. When the temperature of the copolymerexceeds the LCST, the hydrogel collapses, causing a rapid release orburst of any soluble material held within the hydrogel matrix.

The nanoshells serve as heat transfer agents within the polymer matrix.Each of the nanoshells may also include a targeting component, such asan affinity component having an affinity to the cells in the location ofinterest. Being of nanometric diameter, the nanoshells have well definedwavelength absorbance maxima across the visible and infrared range ofthe electromagnetic spectrum. Preferably, the conductive shell of thenanoshells is made of gold. A gold shell can be fabricated, for example,by seeding the amine groups OF the nanostructure core with colloidalgold; additional colloidal gold is added via chemical reduction insolution, to form the gold shell layer.

The wavelength of maximum optical absorption of each nanoshell isdetermined by the ratio of the core radius to the shell thickness. Eachof these variables (core radius and shell thickness) can beindependently controlled during fabrication of the nanoshells. Varyingthe shell thickness, core diameter, and the total diameter of thenanoshell, allows the optical properties of the nanoshells to be tunedover the visible and near-infrared spectrum.

In order to convert light energy into heat, administered nanoshells areexposed to light at an appropriate wavelength (e.g., 800-1200 nm) whichis transmitted through tissue. The generated heat causes collapse of thehydrogel in the vicinity of the nanoshell causes significantly enhancedrelease of chemicals and proteins of varying molecular weight from thenew composite hydrogels.

Since it is capable of converting light energy into heat, the nanoshellof the present invention can be used to induce localized hyperthermia ina cell or tissue of an individual and thus can be utilized astherapeutic agent in treatment of various diseases such ashyperproliferative diseases, as detailed hereinbelow.

For example, an individual having cancer can be administered with atherapeutic effective amount of the nanoshells of the present inventionusing a suitable administration route and thereafter exposed toelectromagnetic radiation in the resonance frequency of the nanoshells,e.g., using a continues wave or pulse laser device, for a time periodof, say, about 5-30 minutes to thereby convert the electromagneticradiation into heat energy. The generated heat may is preferablysufficient to perform therapeutic treatment, e.g., to kill the cells, ifso desired.

Preferably, the electromagnetic radiation is in the near infrared range.Such radiation is advantageous for its ability to penetrate tissue.Other types of radiation can also be used, depending on the selection ofthe conductive shells and the targeted cells. Examples include x-rays,magnetic fields, electric fields and ultrasound.

As stated, the method may be used for destroying living cells. In thisembodiment, each of the nanoshells may include an affinity componenthaving affinity to the living cells to be destroyed. Thus, the presentinvention can be used to treat many types of cancers, such as, but notlimited to, vaginal cancer, vulvar cancer, cervical cancer, endometrialcancer, ovarian cancer, rectal cancer, salivary gland. cancer, laryngealcancer, nasopharyngeal cancer, many lung metastases and acute or chronicleukemia (e.g., lymphocytic, Myeloid, hairy cell).

According to a preferred embodiment of the present invention, theaffinity component of the nanoparticles includes a moiety which may be,for example an antibody, an antigen, a ligand or a substrate.

The following lists primary antibodies known to specifically bind theirassociated cytological markers and which are presently employed asaffinity components in immunohistochemical stains used for research and,in limited cases, for diagnosis and therapy of various diseases.Anti-estrogen receptor antibody (breast cancer), anti-progesteronereceptor antibody (breast cancer), anti-p53 antibody (multiple cancers),anti-Her-2/neu antibody (multiple cancers), anti-EGFR antibody(epidermal growth factor, multiple cancers), anti-cathepsin D antibody(breast and other cancers), anti-Bcl-2 antibody (apoptotic cells),anti-E-cadherin antibody, anti-CA125 antibody (ovarian and othercancers), anti-CA15-3 antibody (breast cancer), anti-CA19-9 antibody(colon cancer), anti-c-erbB-2 antibody, anti-P-glycoprotein antibody(MDR, multi-drug resistance), anti-CEA antibody (carcinoembryonicantigen), anti-retinoblastoma protein (Rb) antibody, anti-rasoncoprotein (p21) antibody, anti-Lewis X (also called CD15) antibody,anti-Ki-67 antibody (cellular proliferation), anti-PCNA (multiplecancers) antibody, anti-CD3 antibody (T-cells), anti-CD4 antibody(helper T cells), anti-CD5 antibody (T cells), anti-CD7 antibody(thymocytes, immature T cells, NK killer cells), anti-CD8 antibody(suppressor T cells), anti-CD9/p24 antibody (ALL), anti-CD10 (alsocalled CALLA) antibody (common acute lymphoblasic leukemia), anti-CD11cantibody (Monocytes, granulocytes, AML), anti-CD13 antibody(myelomonocytic cells, AML), anti-CD14 antibody (mature monocytes,granulocytes), anti-CD15 antibody (Hodgkin's disease), anti-CD19antibody (B cells), anti-CD20 antibody (B cells), anti-CD22 antibody (Bcells), anti-CD23 antibody (activated B cells, CLL), anti-CD30 antibody(activated T and B cells, Hodgkin's disease), anti-CD31 antibody(angiogenesis marker), anti-CD33 antibody (myeloid cells, AML),anti-CD34 antibody (endothelial stem cells, stromal tumors), anti-CD35antibody (dendritic cells), anti-CD38 antibody (plasma cells, activatedT, B, and myeloid cells), anti-CD41 antibody (platelets,megakaryocytes), anti-LCA/CD45 antibody (leukocyte common antigen),anti-CD45RO antibody (helper, inducer T cells), anti-CD45RA antibody (Bcells), anti-CD39, CD100 antibody, anti-CD95/Fas antibody (apoptosis),anti-CD99 antibody (Ewings Sarcoma marker, MIC2 gene product),anti-CD106 antibody (VCAM-1; activated endothelial cells),anti-ubiquitin antibody (Alzheimer's disease), anti-CD71 (transferrinreceptor) antibody, anti-c-myc (oncoprotein and a hapten) antibody,anti-cytokeratins (transferrin receptor) antibody, anti-vimentins(endothelial cells) antibody (B and T cells), anti-HPV proteins (humanpapillomavirus) antibody, anti-kappa light chairis antibody (B cell),anti-lambda light chains antibody (B cell), anti-melanosomes (HMB45)antibody (melanoma), anti-prostate specific antigen (PSA) antibody(prostate cancer), anti-S-100 antibody (melanoma, salvary, glial cells),anti-tau antigen antibody (Alzheimer's disease), anti-fibrin antibody(epithelial cells), anti-keratins antibody, and anti-Tn-antigen antibody(colon carcinoma, adenocarcinomas, and pancreatic cancer).

Other applications of the nanostructures of the present inventioninclude use thereof in biomedical sciences and in biotechnology such astheir use as vehicles for enzyme encapsulation. [Chang (2001) Mol.Biotechnol. 17:249-260], DNA transfection [Kneuer (2000) Bioconj. Chem.11:926-932; Rader (1997) Science 810-814; Koltover (1998) Science281:78-81], scaffolds for tissue building, biosensors [Cao (2002)Science 297:1536-1540; Demers (2002) Science 296:1836-1838; Park (2002)Science 295:1503-1506] and drug delivery [Ulrich (1999) Chem. Rev.99:3181-3198; Lee (2002) Biomacromolecules 3:1115-1119; Murthy (2002) J.Am. Chem. Soc. 124:12398-12399]. For example, drugs can be incorporatedonto the biodegradable nanospheres of the present invention, to therebyallow for timed release of the drug as the nanosphere degrades. Theconditions which allow degradation can be adjusted by varying thechemical bonding within the nanostructure. For example, when acid-labilebonds are used, the nanostructures of the present invention will degradein an acidic environment such as would exist in a site of inflammationor in tumor cells. Alternatively, the nanostructures of the presentinvention can be coated with viral peptide sequences which promotemembrane-permeation. Finally, surface functionalized nanostructures ofthe present invention can also be used to deliver genetic material intoliving cells (i.e., transfection).

In any of the above embodiments, the nanostructures can be coated by anysuitable material, e.g., a conductive material (as in the case of thenanoshells), a semiconductive material or a dielectric material, and canbe bounded to other molecules to achieve desired electrical, mechanical,chemical or biological properties. For example, the nanostructures ofthe present invention can be coated by silver, gold and other conductivematerials.

It is expected that during the life of this patent many relevantstructures of nanometric size will be developed and the scope of theterm nanostructure is intended to include all such new technologies apriori.

As used herein the term “about” refers to ±10%.

Additional objects, advantages, and novel features of the presentinvention will become apparent to one ordinarily skilled in the art uponexamination of the following examples, which are not intended to belimiting. Additionally, each of the various embodiments and aspects ofthe present invention as delineated hereinabove and as claimed in theclaims section below finds experimental support in the followingexamples.

EXAMPLES

Reference is now made to the following examples, which together with theabove descriptions, illustrate the invention in a non limiting fashion.

Generally, the nomenclature used herein and the laboratory proceduresutilized in the present invention include molecular, biochemical,microbiological and recombinant DNA techniques. Such techniques arethoroughly explained in the literature. See, for example, “MolecularCloning: A laboratory Manual” Sambrook et al., (1989); “CurrentProtocols in Molecular Biology” Volumes I-III Ausubel, R. M., ed.(1994); Ausubel et al., “Current Protocols in Molecular Biology”, JohnWiley and Sons, Baltimore, Md. (1989); Perbal, “A Practical Guide toMolecular Cloning”, John Wiley & Sons, New York (1988); Watson et al.,“Recombinant DNA”, Scientific American Books, New York; Birren et al.(eds) “Genome Analysis: A Laboratory Manual Series”, Vols. 1-4, ColdSpring Harbor Laboratory Press, New York (1998); methodologies as setforth in U.S. Pat. Nos. 4,666,828; 4,683,202; 4,801,531; 5,192,659 and5,272,057; “Cell Biology: A Laboratory Handbook”, Volumes I-III Cellis,J. E., ed. (1994); “Current Protocols in Immunology” Volumes I-IIIColigan J. E., ed. (1994); Stites et al. (eds), “Basic and ClinicalImmunology” (8th Edition), Appleton & Lange, Norwalk, Conn. (1994);Mishell and Shiigi (eds), “Selected Methods in Cellular Immunology”, W.H. Freeman and Co., New York (1980); available immunoassays areextensively described in the patent and scientific literature, see, forexample, U.S. Pat. Nos. 3,791,932; 3,839,153; 3,850,752; 3,850,578;3,853,987; 3,867,517; 3,879,262; 3,901,654; 3,935,074; 3,984,533;3,996,345; 4,034,074; 4,098,876; 4,879,219; 5,011,771 and 5,281,521;“Oligonucleotide Synthesis” Gait, M. J., ed. (1984); “Nucleic AcidHybridization” Hames, B. D., and Higgins S. J., eds. (1985);“Transcription and Translation” Hames, B. D., and Higgins S. J., Eds.(1984); “Animal Cell Culture” Freshney, R. I., ed. (1986); “ImmobilizedCells and Enzymes” IRL Press, (1986); “A Practical Guide to MolecularCloning” Perbal, B., (1984) and “Methods in Enzymology” Vol. 1-317,Academic Press; “PCR Protocols: A Guide To Methods And Applications”,Academic Press, San Diego, Calif. (1990); Marshak et al., “Strategiesfor Protein Purification and Characterization—A Laboratory CourseManual” CSHL Press (1996); all of which are incorporated by reference asif fully set forth herein. Other general references are providedthroughout this document. The procedures therein are believed to be wellknown in the art and are provided for the convenience of the reader. Allthe information contained therein is incorporated herein by reference.

Example 1 Nanotubes Self-Assembly of Alzheimer's β-Amyloid CoreRecognition Element

Materials and Experimental Procedures

Material—Peptides (NH₂-Phe-Phe-COOH, SEQ ID NO: 1) were purchased fromBachem (Budendorf, Switzerland). Freshly prepared stock solution wasprepared by dissolving lyophilized form of the peptide in1,1,1,3,3,3,-Hexafluoro-2-propanol at a concentration of 100 mg/ml. Toavoid any pre-aggregation, fresh stock solution were prepared for eachexperiment.

Transmission Electron microscopy (TEM)—Peptide stock solution wasdiluted to a final concentration of 2 mg/ml in double distilled water,then a 10 μl aliquot of the peptide suspension was placed on a 200 meshcopper grid, covered with carbon stabilized formvar film. Following 1minute, excess fluid was removed and the grid was negatively stainedwith 2% uranyl acetate in water. Following 2 minutes of staining, excessfluid was removed from the grid. Samples were viewed in JEOL 1200EXelectron microscope operating at 80 kV.

Scanning Electron microscopy (SEM)—Peptide stock solution was diluted toa final concentration of 0.5 mg/ml in double distilled water. Thereaftera 30 μl aliquot was allowed to dry on microscope glass cover slips. Thesample was than coated with gold. Scanning electron microscopy imageswere made in JSM JEOL 6300 SEM operating at 20 kV.

Congo red staining and birefringence—Peptide stock solutions werediluted to a final concentration of 0.25 mg/ml in double distilledwater. Thereafter a 10 μl aliquot was allowed to dry on glass microscopeslide. Staining was effected by adding a solution of 80% ethanolsaturated with Congo red and NaCl. Birefringence was determined With aSZX-12 Stereoscope (Olympus, Hamburg, Germany), equipped with apolarizing stage.

Dynamic light scattering—Freshly prepared peptide stock solution at aconcentration of 10 mg/ml were diluted in double distilled water to afinal concentration range of 0.01 to 0.5 mg/ml. Experiments wereconducted with protein solutions DynaPro MS-800 instrument (ProteinSolutions, Lakewood, N.J.). Autocorrelation data was fitted usingdynamics V6 software to derive hydrodynamic diameters.

Fourier Transform Infrared Spectroscopy—Infrared spectra were recordedusing Nicolet Nexus 470 FT-IR spectrometer with DTGS detector. Sample ofaged peptide solution, taken from electron microscopy experiment wasvacuum dried on CaF₂ plate to form a thin film. Peptide deposits wereresuspended in double distilled water and dried. The suspensionprocedure was repeated twice to ensure maximal hydrogen to deuteriumexchange. Measurements were effected using a 4 cm⁻¹ resolution and 2000scan averaging. The transmittance minimum values were determined byOMNIC analysis software (Nicolet).

Results

Very concentrated peptide solution (i.e., 100 mg/ml) were prepared bydissolving the lyophilized peptide in 1,1,1,3,3,3 hexafluoro-2-propanol.While the peptide appeared to be highly soluble in the organic solvent,a rapid assembly into ordered semi-crystalline structures was visuallyobserved within seconds after dilution into the aqueous solution at afinal mM concentration range. Assembly into supramolecular structureswas determined within minutes at the μM range, using dynamic lightscattering analysis (data not shown).

Tranmission Electron microscopy indicated that the peptides formwell-ordered, thin (i.e., 50-60 nm in diameter) and elongated (i.e.,several micron long) assemblies (FIG. 9 a). The formed structures wereordered but clearly different from typical amyloid fibrils, as theyformed stiff tubules which lacked a typical branching and curving.Interestingly, these assembies resembled the previously reported tubulesformed by hepta-octopeptides [Vauthey (2002) Proc. Natl. Acad. Sci. USA99:5355].

SEM electron microspcopy was effected to study the tubular structuresformed by the diphenylalanine peptides. As shown in FIG. 9 b, SEManalysis indicated a typical nanotubular structures similar to thosepreviously reported [Vauthey (2002) Proc. Natl. Acad. Sci. USA 99:5355].

To elucidate the molecular configuration of the assembled structures,fourier-transformed infrared spectroscopy was effected. As shown in FIG.9 c, the spectral analysis of the assemblies indicated a sharp 1630 cm⁻¹pick at the amide I region. This pick was consistent with a β-sheet-likeconformation of the single amide bond, as was suggested for peptidenanotubes built from larger building blocks [Ghadiri (1993) Nature366:324; Vauthey (2002) Supra] and for amyloid fibrils [Reches (2002) JBiol Chem 277(38):35475-80].

Congo red staining of the supramoleuclar structures formed by thedipeptides of the present invention showed a green-gold birefringencetypical of amyloid structures (FIG. 9 d).

Altogether, these results show that a small recognition motif of theβ-amyloid polypeptide contains all molecular information required tomediate self-assembly into regular structures. Noteworthy is the factthat the tubular structures were observed with SEM in the absence ofcoating, suggesting that such structures can be used to as conductivetubes.

The persistence length of the nanotubes appeared to be at the order ofmicrometers as evident by the microscopic observation. It is worthnoting, that the formation of the tubular structures was very efficient.Most assemblies, as observed by TEM analysis had tubular structures andalmost no amorphous aggregates were detected (<1%). This is in markdifference to other peptide assemblies (such as amyloid fibrils) inwhich a mixture of ordered and aggregated structures maybe observed.High resolution TEM (HR-TEM; FIG. 10 b) provided further indication ofthe regular structures of the tube walls. The formed structures werehighly ordered and appeared to be rather stiff, but without the usualbranching and curving typical of amyloid fibrils. On the other hand, theassemblies showed some morphological similarity in terms of size andtubular structures to the recently observed peptide nanotubes that areformed by a much longer surfactant-like hepata- to octapeptides [Vauthey(2002) Supra]. These structures are different from the first reportedpeptide nanotubes that were formed by cyclic polypeptides made ofalternating D- and L-amino acids [Hartgerink (1996) J. Am. Chem. Soc.118:43].

Scanning electron microscopy (SEM) was used to further study the tubularstructures (FIGS. 11 a-b). The nanotubes were applied on a glass coverslip coated with gold and imaged by SEM. The low magnificationmicrographs of areas filled with individual nanotubes (FIG. 11 a),substantiated that the tubes were relatively homogenous and evidentlyindividual entities with a persistence length in the order ofmicrometer. FIG. 11 c shows the statistical distribution of thediameters of the nanotubes. In this context, it is worth noting that thecrystal structure of the diphenylalanine peptide, as formed byevaporation of aqueous solution at 80° C., showed a crystal packing ofaligned and elongated long hollows [Gorbitz (2001) Chemistry 38:6791].These structures were also referred to as peptide nanotubes. However, itis very clear from the present structural analysis, that the crystalpacking of the peptide represents a completely different moleculararrangement as compared to the self-assembled individual tubularstructures. Higher magnification SEM analysis also indicated a typicalnanotubular structures that resembled, to some extent, a class ofpeptide nanotubes that were recently reported [Vauthey (2002) supra],albeit apparently stiffer and discrete (FIG. 11 b).

For other applications, such as the assembly of nanotube basedbiosensors or hollow tubing of nanofluidic circuits, enzymaticallystable nanotubes are desired. To assemble such stable tubes,proteolytically stable building blocks based on the D-amino-acidsanalogue of the peptide, NH2-D-Phe-D-Phe-COOH (SEQ ID NO: 8) were used.This peptide formed nanotubes with the same structural features as thecorresponding L-amino-acids peptide (FIG. 12 a). Remarkably, followingone hour of incubation of the peptide with 0.02 mg/ml of Proteinase K,no tubular structures were observed by electron microscopy examination,as compared to hundreds of tubular structures observed prior toproteolysis. In a mark difference, no significant variation could beobserved before and after the incubation of the D-Phe-D-Phe peptide withthe enzyme.

In light of the formation of nanotubes by such short dipeptide, theability of other aromatic dipeptides (e.g., Phe-Trp, Trp-Tyr, Trp-Phc,and Trp-Trp) was tested under similar conditions. As shown in FIG. 12 band FIGS. 13 a-c, nanoscale tubular structures were also observed uponassembly of the Phe-Trp peptide (FIG. 12 b). However, a significantamount of amorphous aggregates were also observed. This is in markdifference to the Phe-Phe peptide in which practically only tubularstructures were observed.

A mechanical model for the formation of the peptide nanotubes describedabove is provided in FIG. 14. Briefly, a stacking interaction betweenaromatic moieties of the peptides is suggested to provide energeticcontribution as well as order aid directionality for the initialinteraction. The spectroscopic evidence of β-sheet conformation of thesingle amide bond is reflected by an extension of the amino acids to theopposite sides and the formation of an extended pleated sheet that isstabilized by hydrogen bonds and aromatic stacking interactions. Theformation of the tubular structures may occur by a closure of theextended sheet as previously suggested [Reches and Gazit (2004) Nanoletters 4: 581-585].

Example 2 Formation of Fullerene-Like Closed-Cage Structures bySelf-Assembly of Aromatic Dipeptides

Materials and Experimental Procedures

Materials—The diphenylalanine and diphenylglycine peptides were purchasefrom Bachen (Bubendorf, Switzerland, SEQ ID NOs: 1 and 6, respectively).The CFF peptide was purchase from SynPep (Dublin Calif., USA). Freshstock solutions of the diphenylalanine and the diphenylglycine wereprepared by dissolving lyophilized form of the peptides in1,1,1,3,3,3-hexafluoro-2-propanol (HFP, Sigma) at a concentration of 100mg/ml.

The CFF peptide was prepared by dissolving lyophilized form of thepeptide in HFP and 25% dithiothreitol, 1 M in ddH20 to a finalconcentration of 25 mg\ml. To avoid any pre-aggregation, fresh stocksolutions were prepared for each experiment. The peptides stocksolutions were diluted into a final concentration of 2 mg/ml in doubledistilled water.

Chemical Modification of an Amine to a Thiol—The diphenylalnine peptidewas dissolved in HFP to a concentration of 100 mg/ml. This was followedby the addition of 2 μl of the solution to 8 μl of 100 mg/ml2-iminothiolane (Sigma) dissolved in dimethylsulfoxide (DMSO) with 2%N,N-diisopropylethylamine (DIAE). Double distilled water was added togive a final peptide concentration of 2 mg/ml. Two control reactionswere effected to exclude components of the reaction mixture in theassembly of the peptides; Essentially, in the first control experimentthe reaction mixture was prepared without the addition of DIAE. In thesecond control experiment, the reaction mixture was prepared without theaddition of DIAE and 2-iminothiolane.

Transmission Electron Microscopy—Following 24 hours of incubation atroom temperature, a 10 μl aliquot of the peptide solution was placed on200 mesh copper grid. After 1 minute, 14 excess fluid was removed. Innegative staining experiments, the grid was stained with 2% uranylacetate in water and after two minutes excess fluid was removed from thegrid. Samples from the chemical reaction that modifies amines to thiolswere not negatively stained with uranyl acetate. Samples were viewedusing a JEOL 1200EX electron microscope operating at 80 kV.

Atomic Force Microscopy—AFM samples were prepared by drying the peptidesolutions on TEM grids, without the staining procedure. Semicontact modeimaging was performed on a P47 solver—NT-MDT (Moscow, Russia), by usingOTESP integrated cantilever probes with resonance frequency 390 kHz.

High Resolution Scanning Electron Microscopy—TEM grids that were usedfor AFM analysis were viewed using JSM-6700 Field Emission ScanningElectron Microscope equipped with cold filed emission gun operating at 1kV.

Stability in Alkaline and Acidic Conditions—In the case of stability toalkaline conditions, NaOH was added into the peptide nanosphere solutionto a final concentration of 1 M NaOH. In the case of stability in acidicconditions, TFA was added to the nanostructure solution to a finalconcentration of 10% TFA. After 5 hours peptide solutions were placed onTEM grids and analyzed by TEM.

Results

In search for the simplest biomolecular self-assembled system, the mostgeneric form of an aromatic dipeptide, the diphenylglycine was designedand synthesized (FIG. 15 b). The diphenylglycine offers similarmolecular properties as the diphenylalanine peptide albeit its molecularstructure is more rigid with a lower degree of freedom due to the lackof rotational freedom around the additional C—C bond and the highersteric hindrance of the molecule.

Structural analysis using TEM (transmission electron microscopy)revealed that under the same conditions that peptide nanotubes wereformed by the diphenylalanine, spherical nanometric structuresself-assembled by the diphenylglycine peptide (FIGS. 15 c-d). Thesenanometric particles existed as individual entities and had a uniformspherical appearance as seen by TEM visualization (FIG. 15 d). Theassembly of the spherical particles was very efficient and regular, ascould be seen using low magnification TEM analysis (FIG. 15 d). Theefficiency and regularity were similar to those observed with thepeptide nanotubes (see Example 1, above).

In order to further examine the three dimensional characteristics of thenovel nanoparticles they were subjected to analysis by SEM (scanningelectron microscopy). Cold field emission gun (CFEG) high-resolutionscanning electron microscope (HRSEM) confirmed the three dimensionalspherical shape and the regularity of the self assembled nanostructures(FIG. 16 a).

In addition, AFM (atomic force microscopy) analysis was employed to getan independent indication about the topography of nanostructures. TheAFM analysis clearly confirmed the three dimensional sphericalconfiguration of the nanostructures (FIGS. 16 b-c).

It will be appreciated that while AFM is a less suitable tool todetermine the exact dimensions of the structures at the horizontal andvertical axis due to tip convolution, it is an excellent method todetermine the height of nanostructures at the Z-range. Indeed, AFManalysis clearly indicated that the spheres are about 90 nm in height(FIG. 16 b), which is consistent with both TEM and SEM analysis.

The stability of the newly discovered nanoparticles under extremechemical conditions was addressed as well (FIGS. 17 a-b). Thenanospheres were found to be stable under acidic conditions followingincubation for 5 hours at 10% TFA as they maintained their configurationand uniform structure (FIG. 17 a). The stability of the nanospheres wasalso tested under alkaline conditions i.e., 1M NaOH for 5 hours (FIG. 17b). In the presence of NaOH, the nanosphere structure appeared to bemore uniform while having a smaller diameter. This remarkable stabilityof the nanoparticles is very intriguing both from the scientific pointof view as well as the technological one. The significant stability ofthe peptide nanostructures is rare but consistent with the structuralstability of amyloid fibrils as was recently reported [Scheibel (2003)Proc. Natl. Acad. Sci. USA 100:4527].

These results are in accordance with the apparent role of peptide motifsin the molecular recognition and self-assembly of amyloid fibrils.Moreover, the unusual stability of the peptide nanostructures isextremely useful for their use as part of a combined (bio)organic and/orinorganic nanoscale fabrication process, including optic andelectron-beam lithographic protocols. Although biologically basedscaffolds offer many advantages to nanotechnology, their relativeinstability in general questions their ability to serve in robust andlong-lasting nanodevices.

The newly described peptide nanostructures offer both molecularrecognition and chemical flexibility of biological nano-objects,together with stability that is compatible with industrial proceduresand the requirements for robust and stable devices.

In parallel experiments, the ability of the cysteinediphenylalaninetripeptide (CFF, SEQ ID NO: 7, FIG. 18 a) to form peptide nanotubes wasaddressed. The rationale behind these studies was to introduce a thiolgroup into the nanotubes that would allow their covalent attachment tofabricated gold electrodes in nanodevices. However, as shown in FIGS. 18b-c, CFF peptide did not self-assemble into nanotubes but rather intonanospheres that were very similar to those formed by thediphenylglycine peptide.

To study whether the spherical structures that were formed by the CFFpeptide were the result of the peptide length or rather the presence ofthe thiol group, an amine was chemically modified into a thiol in thecontext of the diphenylalanine peptide (FIG. 18 d). For that purpose,2-iminothiolane (Traut's reagent), which reacts with the single primaryamine in the diphenylglycine and introduces a sulfhydryl group was used.The peptide was reacted with the reagent in organic solvent mixture thatwas then followed by dilution into an aqueous solution that allowed theself-assembly process. As shown in FIG. 18 d, the addition of a thiolgroup to the diphenylalnine peptide transformed the geometry of theassembled structures from nanotubular into spherical ones. As a control,the same reaction mixture was used but without the addition of theN,Ndiisopropylethylamine base that is required for the reaction. Underthese conditions only nanotubular structures were observed.

The study of inorganic nanotubes and fullerene-like structures,indicated that the formation of fullerenes is not unique to carbon andis attributed to a genuine property of two-dimensional (i.e., layered)compounds [Tenne (1992) Nature 360:444; Feldman (1995) Science 267:222;Chhowalla (2000) Nature 407:164; Tenne (2002) Chemistry 23:5293].

As meniotned hereinabove, it is highly likely that the novel type ofpeptide nanotubes is being formed by a closure of a two dimensionallayer. The results described herein provide further experimental supportto this notion. It appears that the energetic contribution provided bythe disulphide bridge formation may allow closure of the two-dimensionallayer into more closely packed spherical structures. Taken together,there results clearly suggest that aromatic peptide assemblies representa novel class of nanostructures that are mechanistically closely-relatedto aromatic carbon nanotubes and fullerenes and to their relatedinorganic nanotubes and fullerene-like structures. Applications,methodologies, and theories that were applied to the study of carbon andinorganic nanostructures should be of great importance for futureexploration and utilization of the peptide nanostructures. Theseproperties of the peptide nanostructures, taken together with theirbiological compatibility and remarkable thermal and chemical stability,may provide very important tools for future nanotechnology applications.

Example 3 Formation of Tubular Nanostructures by Self-Assembly ofPolyphenylalanine Peptide

The ability of polyphenylalanine peptides of 50-136 amino acids to selfassemble into discrete nanotubes was examined.

Materials and Experimental Procedures

Materials—The Polyphenylalanine peptide was purchase from Sigma-Aldrich.Fresh stock solution was prepared by dissolving lyophilized form of thepeptide in dichloroacetic acid at a concentration of 5 mg/ml and wasincubated for an hour in a water bath pre heated to 85° C. To avoid anypre-aggregation, fresh stock solutions were prepared for eachexperiment. The peptide stock solution was diluted into double-distilledwater to a final concentration of 2.5 mg/ml.

Scanning electron microscopy—A 30 μl suspension of 1 day aged peptidesolution was dried at room temperature on a microscope glass cover slipand coated with gold. Scanning electron microscopy images were madeusing a JSM JEOL 6300 SEM operating at 20 kV,

Congo red (CR) staining and birefringence—A 1.0 μl suspension of a 1 dayaged peptide solution was allowed to dry overnight on a glass microscopeslide. Staining was preformed by the addition of 10 μl solution of 80%ethanol saturated with CR and NaCl. The slide was allowed to dry for afew hours at room temperature. Birefringence was determined with aSZX-12 Stereoscope equipped with cross-polarizes.

Fourier transform infrared spectroscopy—Infrared spectra were recordedusing Nicolet Nexus 470 FT-IR spectrometer with a DGTS detector. A 30 μlsuspension of 1 day aged polypeptide solution was dried by vacuum on aCaF₂ plate to form thin film. The peptide deposits was resuspended indouble distilled water and dried. The resuspension procedure wasrepeated twice to ensure maximal hydrogen to deuterium exchange. Themeasurements were taken using a 4 cm⁻¹ resolution and 2000 scansaveraging. The transmittance minima values were determined by OMNICanalysis program (Nicolet).

Results

As shown in FIG. 19 a structural analysis using SEM (scanning electronmicroscopy) showed that under similar conditions by which peptidenanotubes were formed by the diphenylalanine, tubular nanometricstructures self-assembled by polyphenylalanine peptides of 50-136 aminoacid residues. These nanometric particles existed as individual entitiesand their assembly was very efficient. The efficiency and homogeneitywere similar to those observed with the peptide nanotubes self assembledby diphenylalanine peptides (see Example 1 above). Nanotubes ofpolyphenylalanine showed an apple green birefringence as seen upon Congored sating and visualization under crossed polarized light (FIG. 19 b).An amide I FT-IR spectrum of the polyphenylalanine solution exhibited aminimum at 1632 cm⁻¹ that is indicative of a parallel β-sheet structure(FIG. 19 c). These properties are consistent with biophysical propertiesof peptide nanotubes self assembled by diphenylalanine peptides.

Example 4

Tubular nanostructures were formed from naphthylalanine-naphthylalanine(Nal-Nal) dipeptides, in accordance with preferred embodiment of thepresent invention. The Chemical structure of the Nal-Nal dipeptide isschematically shown in FIG. 20.

Fresh stock solutions of Nal-Nal dipeptides were prepared by dissolvinglyophilized form of the peptides in 1,1,1,3,3,3-hexafluoro-2-propanol(HFIP, Sigma) at a concentration of 100 mg/mL. To avoid anypre-aggregation, fresh stock solutions were prepared for eachexperiment.

The peptides stock solutions were diluted into a final concentration of2 mg/mL in double distilled water, then the samples were placed on 200mesh copper grid, covered by carbon stabilized formvar film. Following 1minute, excess fluid was removed and the grid was negatively stainedwith 2% uranyl acetate in water. Following 2 minutes of staining, excessfluid was removed from the grid. Samples were viewed in JEOL 1200EXelectron microscope operating at 80 kV.

FIG. 21 is an electron microscope image of the samples, captured a fewminutes after the dilution of the peptide stock into the aqueoussolution. As shown, the dipeptides form thin (from several nanometers toa few tens of nanometers in diameter) and elongated (several microns inlength) tubular structures.

Example 5

Tubular and planar nanostructures were formed from by four differentdipeptides, in accordance with preferred embodiment of the presentinvention.

The following dipeptides were used:(Pentafluro-Phenylalanine)-(Pentafluro-Phenylalanine),(Iodo-Phenylalanine)-(Iodo-Phenylalanine), (4-Phenylphenylalanine)-(4-Phenyl phenylalanine) and(P-nitro-Phenylalanine)-(P-nitro-Phenylalanine).

For the first two dipeptides[(Pentafluro-Phenylalanine)-(Pentafluro-Phenylalanine) and(Iodo-Phenylalanine)-(Iodo-Phenylalanine)] fresh stock solutions wereprepared by dissolving lyophilized form of the peptides in DMSO at aconcentration of 100 mg/mL.

For the third and fourth dipeptides [(4-Phenyl phenylalanine)-(4-Phenylphenylalanine) and (P-nitro-Phenylalanine)-(P-nitro-Phenylalanine)],fresh stock solutions were prepared by dissolving lyophilized form ofthe peptides in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP, Sigma) at aconcentration of 100 mg/mL. To avoid any pre-aggregation, fresh stocksolutions were prepared for each experiment.

The peptides stock solutions were diluted into a final concentration of2 mg/mL in double distilled water.

In the case of (P-nitro-Phenylalanine)-(P-nitro-Phenylalanine) the finalconcentration was 5 mg/mL.

Subsequently, the samples were placed on 200 mesh copper grid, coveredby carbon stabilized formvar film. Following 1 minute, excess fluid wasremoved and the grid was negatively stained with 2% uranyl acetate inwater. Following 2 minutes of staining, excess fluid was removed fromthe grid. Samples were viewed in JEOL 1200EX electron microscopeoperating at 80 kV.

FIGS. 22A-D are electron microscope images of the four samples, captureda few minutes after the dilution of the peptide stock into the aqueoussolution.

FIG. 22A shows tubular assemblies formed by the(Pentafluro-Phenylalanine)-(Pentafluro-Phenylalanine) dipeptide, FIG.22B shows tubular structures assembled by(Iodo-Phenylalanine)-(Iodo-Phenylalanine), FIG. 22C shows planarnanostructures formed by (4-Phenyl phenylalanine)-(4-Phenylphenylalanine), and FIG. 22D shows fibrilar assemblies of(P-nitro-Phenylalanine)-(P-nitro-Phenylalanine).

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable sub combination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

1. A tubular, spherical or planar nanostructure composed of a pluralityof peptides, wherein each of said plurality of peptides includes no morethan 4 amino acids and whereas at least one of said 4 amino acids is anaromatic amino acid.
 2. The tubular, spherical or planar nanostructureof claim 1, wherein the nanostructure does not exceed 500 nm indiameter.
 3. The tubular, spherical or planar nanostructure of claim 1,wherein the tubular nanostructure is at least 1 nm in length.
 4. Thetubular, spherical or planar nanostructure of claim 1, wherein each ofsaid 4 amino acids is independently selected from the group of naturallyoccurring amino acids, synthetic amino acids and combinations thereof.5. The tubular, spherical or planar nanostructure of claim 1, wherein atone peptide of said plurality of peptides comprises at least twoaromatic amino acids.
 6. The tubular, spherical or planar nanostructureof claim 5, wherein at one peptide of said plurality of peptides is ahomodipeptide.
 7. The tubular, spherical or planar nanostructure ofclaim 6, wherein each of the amino acids is said homodipeptide comprisesan aromatic moiety.
 8. The tubular, spherical or planar nanostructure ofclaim 7, wherein said aromatic moiety is selected from the groupconsisting of substituted or unsubstituted naphthalenyl and substitutedor unsubstituted phenyl.
 9. The tubular, spherical or planarnanostructure of claim 8, wherein said substituted phenyl is selectedfrom the group consisting of pentafluoro phenyl, iodophenyl, biphenyland nitrophenyl.
 10. The tubular, spherical or planar nanostructure ofclaim 8, wherein said homodipeptide is selected from the groupconsisting of naphthylalanine-naphthylalanine dipeptide,(pentafluro-phenylalanine)-(pentafluro-phenylalanine) dipeptide,(iodo-phenylalanine)-(iodo-phenylalanine) dipeptide, (4-phenylphenylalanine)-(4-phenyl phenylalanine) dipeptide and(p-nitro-phenylalanine)-(p-nitro-phenylalanine) dipeptide.
 11. Thetubular, spherical or planar nanostructure of claim 1, wherein at leastone of said 4 amino acids is a D-amino acid.
 12. The tubular, sphericalor planar nanostructure of claim 1, wherein at least one of said 4 aminoacids is an L-amino acid.
 13. The tubular, spherical or planarnanostructure of claim 1, wherein the nanostructure is stable at atemperature range of 4-400° C.
 14. The tubular, spherical or planarnanostructure of claim 1, wherein the nanostructure is stable in anacidic environment.
 15. The tubular, spherical or planar nanostructureof claim 1, wherein the nanostructure is stable in a basic environment.16. A nanostructure composed of a plurality of polyaromatic peptides.17. The nanostructure of claim 16, wherein said polyaromatic peptidesare selected from the group consisting of polyphenylalanine peptides,polytriptophane peptides, polytyrosine peptides, non-natural derivativesthereof and combinations thereof.
 18. The nanostructure of claim 16,wherein said polyaromatic peptides are at least 30 amino acids inlength.
 19. A method of generating a tubular, spherical or planarnanostructure, the method comprising incubating a plurality of peptidemolecules under conditions which favor formation of the tubular,spherical or planar nanostructure, wherein each of said peptidemolecules includes no more than 4 amino acids and whereas at least oneof said 4 amino acids is an aromatic amino acid.
 20. The method of claim19, wherein the tubular, spherical or planar nanostructure does notexceed 500 nm in diameter.
 21. The method of claim 19, wherein thenanotube is at least 1 nm in length.